Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide,causing nearly 600 000 deaths each year.Increased risk of HCC due to chronicinfection with hepatitis B virus (HBV) and exposure to dietary aflatoxins is respon-sible for many of these deaths.Prevention strategies targeting HBV infection andaflatoxin exposure could dramatically impact the rates of HCC.Universal HBVvaccination programs have begun in some high-risk areas.Strategies to reduceaflatoxin contamination in food stores have also been implemented.However,complete elimination of aflatoxin contamination might not be possible.For thisreason,chemoprevention strategies which alter aflatoxin disposition are a practi-cal strategy to reduce the incidence of HCC in populations with high dietaryaflatoxin exposure.The mechanisms of aflatoxin-induced hepatocarcinogenesisare well known.This knowledge provides the basis for evaluation of both expo-sures to aflatoxin,as well as modulation of aflatoxin disposition by chemopreventiveagents.Products of aflatoxin DNA damage and toxicity as well as other metabo-lites can be used as biomarkers to evaluate modulation of aflatoxin disposition.Modulation of aflatoxin disposition can be achieved through induction of conju-gating and cytoprotective enzymes.Many of these enzymes are regulated throughKelch ECH-associating protein 1 (Keap1)-NF-E2-related factor 2(Nrf2)-antioxi-dant response element (ARE) signaling,making this pathway an important mo-lecular target for chemoprevention.Rodent studies have identified several classesof chemopreventive agents which induce cytoprotective genes.These inducersinclude phenolic antioxidants,dithiolethiones,isothiocyanates,and triterpenoids.Furthermore,clinical interventions have shown that inducers of Keap 1-Nrf2-ARE signaling increase cytoprotective enzyme expression,resulting in modula-tion of aflatoxin disposition.Much work remains to be done in order to takepromising chemopreventive agents from preclinical evaluation to application inat-risk populations.However,appropriately designed clinical trials will aid in thisprocess,which can have profound impact on the incidence of HCC. Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, causing nearly 600 000 deaths each year. Increased risk of HCC due to chronic infection with hepatitis B virus (HBV) and exposure to dietary aflatoxins is responsibly for many of these deaths .Prevention strategies targeting HBV infection andaflatoxin exposure could dramatically impact the rates of HCC.Universal HBVvaccination programs have begun in some high-risk areas. Strategies to reduceaflatoxin contamination in food stores have also been implemented. However, complete elimination of aflatoxin contamination might not be possible.For thisreason, chemoprevention strategies which alter aflatoxin disposition are a practi-cal strategy to reduce the incidence of HCC in populations with high dietaryaflatoxin exposure.The mechanisms of aflatoxin-induced hepatocarcinogenesis well known. this knowledge provides the basis for evaluation of both expo -sures to aflatoxin, as well as modulation of aflatoxin disposition by chem opreventive agents. Products of aflatoxin DNA damage and toxicity as well as other metabo-lites can be used as biomarkers to evaluate modulation of aflatoxin disposition. Modulation of aflatoxin disposition can be achieved through induction of conju-gating and cytoprotective enzymes. regulated through Kelch ECH-associating protein 1 (Keap1) -NF-E2-related factor 2 (Nrf2) -antioxi-dant response element (ARE) signaling, making this pathway an important mo- lecular target for chemoprevention chemopreventive agents which induce cytoprotective genes. These inducersinclude phenolic antioxidants, dithiolethiones, isothiocyanates, and triterpenoids. Future and clinical interventions have shown that inducers of Keap 1-Nrf2-ARE signaling increase cytoprotective enzyme expression, resulting in modula tion of aflatoxin disposition. Much work remains to be done in order to takepromising chemopreventive agents from preclinical evaluation toapplication inat-risk populations.However, Preferred designed clinical trials will aid in thisprocess, which can have profound impact on the incidence of HCC.