Inclusion Criteria:
* Subjects must give informed consent to this study before the trial and voluntarily sign a written informed consent form.
* Age 18 to 75 (inclusive), gender is not limited.
* Patients with advanced primary hepatocellular carcinoma confirmed by histopathology or cytology.
* According to the CSCO Guidelines for the Diagnosis and Treatment of Primary Liver Cancer (2022 Edition), patients who have received at least previous first-line treatment regimens that have failed treatment (disease progression or inability to tolerate treatment) must have been treated.
* According to RECIST 1.1, it is determined that at least one CT examination shows that it is measurable and meets the requirements of the volume of injection administration (or the volume of first injection administration in phase IIa) that can be injected under ultrasound guidance (preferably the main tumor burden lesion) under ultrasound guidance, and the longest baseline diameter of the injection lesion (short diameter of lymph node lesions) is \>1.5 cm (of which the portal vein lymph node is short, the diameter needs to be \> 20 mm).
* Those with positive herpes simplex virus antibody test results (HSV-1 IgG or HSV-1 IgM).
* ECOG physical status score 0-1.
* Estimated survival time of more than 3 months.
* Have adequate organ function:
1. Routine blood (no blood transfusion or colony-stimulating factor therapy within 14 days): ANC≥ 1.5×109/L, PLT≥75×109/L, Hb≥85g/L, lymphocyte count ≥1.5×109/L (for lymphocyte count 0.8×109/L to 1.5×109/L is determined by the investigator whether to enroll);
2. Liver function: TBIL≤1.5×ULN, ALT≤5×ULN, AST≤5×ULN;
3. Child-Pugh A or better B (≤ 7);
4. Renal function: Cr≤1.5×ULN, and creatinine clearance ≥ 45ml/min (calculated according to Cockcroft-Gault formula);
5. Coagulation function: activated partial thromboplastin time (APTT) ≤ 1.5×ULN, international normalized ratio (INR) ≤1.5×ULN.
* Eligible subjects of childbearing potential (male and female) must agree to use a reliable method of contraception (hormonal or barrier or abstinence) during the trial and at least 90 days after the last dose (VG161 or carrelizumab, whichever occurs later); Female patients of childbearing age must have a negative blood pregnancy test within 7 days prior to enrollment.
Exclusion Criteria:
* Known fibrolamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, cholangiocarcinoma or mixed hepatocellular carcinoma.
* Have received chemotherapy, radiotherapy, biological therapy, endocrine therapy, targeted therapy, immunotherapy and other anti-tumor drugs within 4 weeks before the first use of study drugs, among which oral fluorouracils and small molecule targeted drugs are the first use of study drugs. Within the first 2 weeks or the 5 half-lives of the drug (whichever is longer).
* Have received other unmarketed clinical trial treatments within 4 weeks before using the study drug for the first time.
* Have undergone major organ surgery (excluding puncture biopsy) or experienced significant trauma within 4 weeks before taking the study drug for the first time.
* Patients who have received systemic corticosteroids (prednisone \>10 mg/day or equivalent doses of similar drugs) or other immunosuppressants within 14 days before the first use of study drugs;Exceptions are the following: treatment with topical, ocular, intraarticular, intranasal, and inhaled corticosteroids; short-term use of corticosteroids (≤10 mg prednisone equivalent) for prophylactic treatment (e.g., prevention of contrast media allergy).
* Have received vaccination within 4 weeks before the first use of study drugs.
* Known severe allergic reaction to any monoclonal antibody.
* The adverse reactions of previous anti-tumor treatments have not returned to CTCAE 5.0 grade ≤1 (except for toxicities such as hair loss that the researcher has judged to have no safety risks).
* Liver tumor burden is greater than 50% of the total liver volume, or those who have received liver transplantation in the past.
* Patients with central nervous system metastasis, spinal cord metastasis and/or spinal cord compression are not suitable for inclusion according to the investigator's judgment.
* In the period of recurrent infection of herpes simplex virus, with corresponding clinical manifestations, such as cold sores, herpetic keratitis, herpetic dermatitis, genital herpes, etc.
* Other uncontrolled active infections.
* Have a history of immunodeficiency, including positive HIV antibody test and positive Treponema pallidum antibody test.
* Patients with active chronic hepatitis B or active hepatitis C (except hepatitis B virus carriers, stable hepatitis B after drug treatment \[negative HBV-DNA test or \<50IU/ml\] and cured hepatitis C patients \[HCV RNA Tested negative\]).
* Have a history of serious cardiovascular and cerebrovascular diseases:
1. Ventricular arrhythmias requiring clinical intervention;
2. QTc interval\>480ms;
3. Acute coronary syndrome, congestive heart failure, stroke or other grade III or above cardiovascular events within 6 months;
4. New York Heart Association (NYHA) cardiac function class ≥ class II or left ventricular ejection fraction (LVEF) \<40%;
5. Uncontrolled hypertension (systolic blood pressure ≥140mmHg, or diastolic blood pressure ≥90mmHg after treatment).
* Patients with active or past autoimmune diseases that may relapse (such as interstitial pneumonia, colitis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism (including but not limited to these diseases or syndromes, etc.); but does not include patients with clinically stable autoimmune thyroiditis, autoimmune-mediated hypothyroidism treated with a stable dose of thyroid replacement hormone; Type I diabetes on insulin; patients with vitiligo or childhood asthma/allergies that have resolved and do not require any intervention in adulthood.
* Have received immunotherapy and experienced immune-related adverse events (irAEs) such as immune-related pneumonia, myocarditis, etc., which may affect the safety of the trial medication as judged by the researcher.
* Known alcohol or drug dependence.
* People with mental disorders or poor compliance.
* Pregnant or lactating women.
* Patients with obvious symptoms and unstable pleural effusion, peritoneal effusion or pericardial effusion (those with stable clinical symptoms after treatment of pleural effusion, ascites or pericardial effusion can be included).
* The researcher believes that the subject has other serious systemic diseases or other reasons and is not suitable to participate in this clinical study.
