Inclusion Criteria:
* Male or female current tobacco smokers with \>= 20 pack years of self-reported smoking exposure and a current average use of \>= 10 cigarettes/day
* Age \>= 18 years. No upper age limit
* Karnofsky performance scale \>= 70%
* Absolute neutrophil count \>= 1,000/microliter
* Platelets \>= 100,000/microliter
* Total bilirubin =\< 2 x institutional upper limit of normal (ULN)
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3 x ULN
* Creatinine =\< 1.5 x ULN
* Participants with known human immunodeficiency virus (HIV) infection are not eligible for this trial due to potential interaction between sulforaphane and anti-retroviral therapy
* Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. Participants with HCV infection who are currently on treatment are not eligible due to potential interaction between sulforaphane and anti-retroviral therapy
* The effects of BSSE on the developing human fetus at the recommended therapeutic dose are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately
* Ability to understand and the willingness to sign a written informed consent document
Exclusion Criteria:
* History of invasive cancer within the past 2 years, except for excised and cured non-melanoma skin cancer or carcinoma in situ of the cervix. Participants who continue adjuvant treatment for an index cancer occurring \> 2 years ago, such as adjuvant hormonal therapy for breast cancer, are excluded. Participants who are on anti-neoplastic treatment for a chronic malignancy, such as multiple myeloma or chronic myelogenous leukemia, are excluded
* Ongoing use of a nutraceutical or dietary supplement containing glucoraphanin or sulforaphane
* Note, participants will be eligible if they agree to stop the glucoraphanin or sulforaphane product at least 7 days prior to the baseline visit (7-day washout)
* Participants with known chronic hepatitis B virus (HBV) infection are not eligible for this trial due to potential interaction between sulforaphane and suppressive anti-viral therapy
* Participants may not be receiving any other investigational agents
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to Avmacol ES® (BSSE)
* Uncontrolled intercurrent illness including, but not limited to, serious ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia
* Any other condition or lifestyle factor, that, in the opinion of the principal investigator, may adversely affect the participant's ability to complete the study or its measures or pose significant risk to the participant
* Pregnant or lactating women. Pregnant women are excluded from this study because the effects of BSSE on the developing human fetus are unknown. Because there is an unknown but potential risk for adverse events (AEs) in nursing infants secondary to treatment of the mother with BSSE, Breastfeeding should be discontinued if the mother is treated with BSSE
