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About 42,030 cases in the United States in 2019, but worldwide this may be the most common tumor; 31,780 deaths in 2019 in the United States. Male:female = 4:1; tumor usually develops in cirrhotic liver in persons in fifth or sixth decade. High incidence (and increasing) in Asia and Africa is related to etiologic relationship between this cancer and hepatitis B and C infections. Effective vaccines for hepatitis B prevention and successful chemotherapy of hepatitis C should reduce the incidence. Aflatoxin exposure contributes to etiology and leaves a molecular signature, a mutation in codon 249 of the gene for p53. Mutations in TERT (telomerase reverse transcriptase) promoter and CTNNB1 (beta-catenin gene) are common.