Inclusion Criteria:
Participants must meet all of the following inclusion criteria to be enrolled in this trial:
1. Voluntarily sign the written informed consent form.
2. Age 18 to 80 years (inclusive), male or female.
3. Histologically or cytologically confirmed Hepatocellular Carcinoma (HCC) according to the "Clinical Practice Guideline for Primary Liver Cancer (2024 Edition)," and evaluated by a Multi-Disciplinary Team (MDT) as initially unresectable.
4. No prior systemic anti-tumor therapy (including targeted therapy, immunotherapy, and systemic chemotherapy).
5. Barcelona Clinic Liver Cancer (BCLC) stage C and China Liver Cancer (CNLC) stage IIIa, complicated with imaging-confirmed Vp3 portal vein tumor thrombus (PVTT, defined as tumor thrombus invading the first-order branches of the portal vein but not the main trunk).
6. At least one measurable target lesion according to RECIST v1.1 criteria.
7. Expected survival time of ≥ 3 months.
8. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 or 1.
9. Child-Pugh liver function class A or B (score ≤ 7).
10. Adequate major organ function, meeting the following baseline laboratory criteria:
* Hematology: Hemoglobin ≥ 90 g/L; Absolute Neutrophil Count (ANC) ≥ 1.5 x 10\^9/L; Platelet count ≥ 75 x 10\^9/L.
* Biochemistry: Albumin ≥ 28 g/L; Total Bilirubin ≤ 3 x Upper Limit of Normal (ULN); AST and ALT ≤ 5 x ULN; Alkaline Phosphatase (ALP) ≤ 5 x ULN; Serum Creatinine ≤ 1.5 x ULN.
* Coagulation: INR or Prothrombin Time (PT) ≤ 1.5 x ULN; Activated Partial Thromboplastin Time (APTT) ≤ 1.5 x ULN.
11. Women of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to enrollment, must not be breastfeeding, and must agree to use highly effective contraception during the study treatment and for at least 6 months after the last dose.
12. Good compliance and willingness to cooperate with all study-related follow-up procedures.
13. Assessed by the MDT as "Potentially Resectable" according to the "Chinese expert consensus on conversion and perioperative therapy of primary liver cancer (2024 edition)". This is defined as participants who are temporarily unsuitable for upfront surgical resection due to oncological factors (e.g., Vp3 PVTT indicating a high risk of early post-operative recurrence) or technical factors (e.g., massive tumor size leading to insufficient future liver remnant \[FLR\]), but who are expected to convert to an R0 resection and achieve significant clinical benefit following downstaging with the combination of FOLFOX-HAIC and systemic therapy.
Exclusion Criteria:
Participants who meet any of the following criteria will be excluded from the study:
1. History of other active malignancies within 5 years (except for adequately treated basal cell carcinoma of the skin or papillary thyroid cancer).
2. Evidence of extrahepatic metastasis confirmed by chest, abdomen, and pelvis CT and/or MRI scans.
3. Presence of clinically significant ascites.
4. History of hepatic encephalopathy.
5. History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on chest CT scan at screening.
6. Severe infection within 4 weeks prior to enrollment, including but not limited to hospitalization due to infectious complications, bacteremia, or severe pneumonia.
7. History of hypertensive crisis; or major cardiovascular disease within 3 months prior to starting study treatment (e.g., New York Heart Association \[NYHA\] Class II or worse heart failure, myocardial infarction, cerebrovascular accident, unstable arrhythmia, or unstable angina).
8. Inadequately controlled arterial hypertension, defined as systolic blood pressure (BP) ≥ 150 mmHg and/or diastolic BP \> 100 mmHg (based on an average of ≥ 3 BP readings obtained from ≥ 2 measurements). Achieving these parameters through the use of antihypertensive therapy is permitted.
9. Severe vascular disease within 6 months (e.g., aortic aneurysm requiring surgical repair or peripheral arterial thrombosis); or a current or recent history of active autoimmune disease or immunodeficiency (including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, or multiple sclerosis).
10. Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of the investigational drugs, may affect the interpretation of the results, or may place the patient at high risk for treatment-related complications.
11. Use of systemic immunosuppressive medications within 2 weeks prior to the first dose of study treatment, or the expected need for long-term systemic immunosuppressive therapy during the study. Exceptions permitting the use of corticosteroids include: (1) prophylactic use to prevent allergic reactions to imaging contrast media (e.g., short-term dexamethasone); (2) topical, ophthalmic, intra-articular, otic, or inhaled corticosteroids with minimal systemic absorption; (3) physiological replacement doses of systemic corticosteroids (defined as ≤ 10 mg/day of prednisone or an equivalent corticosteroid).
12. Evidence of bleeding diathesis or severe coagulopathy.
13. Patients preparing to undergo, or who have previously received, a solid organ or allogeneic bone marrow transplant.
