Aflatoxin, a toxin produced by fungi Aspergillus flavus and Aspergillus parasiticus, is a known human liver carcinogen. Hepatocellular carcinoma (HCC), or liver cancer, is the third leading cause of cancer deaths globally, with higher prevalence in developing countries. Aflatoxin exposure is a significant risk factor for HCC, especially in populations with high hepatitis B virus (HBV) prevalence. A quantitative risk assessment estimated that 25,200–155,000 new HCC cases annually may be attributable to aflatoxin exposure, with most cases occurring in sub-Saharan Africa, Southeast Asia, and China. Aflatoxin exposure is synergistic with HBV in increasing HCC risk, and the risk is higher in rural populations where aflatoxin contamination is more prevalent. Aflatoxin exposure is a controllable risk factor, but many affected regions lack the resources to implement control strategies. Public health interventions, including vaccination against HBV, can reduce aflatoxin-related HCC risk. The study highlights the significant role of aflatoxin in contributing to global liver cancer burden, emphasizing the need for interventions to reduce aflatoxin exposure and HBV prevalence in high-risk regions.Aflatoxin, a toxin produced by fungi Aspergillus flavus and Aspergillus parasiticus, is a known human liver carcinogen. Hepatocellular carcinoma (HCC), or liver cancer, is the third leading cause of cancer deaths globally, with higher prevalence in developing countries. Aflatoxin exposure is a significant risk factor for HCC, especially in populations with high hepatitis B virus (HBV) prevalence. A quantitative risk assessment estimated that 25,200–155,000 new HCC cases annually may be attributable to aflatoxin exposure, with most cases occurring in sub-Saharan Africa, Southeast Asia, and China. Aflatoxin exposure is synergistic with HBV in increasing HCC risk, and the risk is higher in rural populations where aflatoxin contamination is more prevalent. Aflatoxin exposure is a controllable risk factor, but many affected regions lack the resources to implement control strategies. Public health interventions, including vaccination against HBV, can reduce aflatoxin-related HCC risk. The study highlights the significant role of aflatoxin in contributing to global liver cancer burden, emphasizing the need for interventions to reduce aflatoxin exposure and HBV prevalence in high-risk regions.