Morbidity and mortality from hepatocellular carcinoma (HCC), which is primarily caused by hepatitis B virus or hepatitis C virus, can be prevented. Public health interventions have eliminated transfusion transmission of these viruses and, in endemic countries with effective hepatitis B virus vaccination programs, have greatly reduced incident hepatitis B virus infections (and HCC) in children. Antiviral treatment can eliminate detectable hepatitis C virus in 50%-80% of chronically infected patients, presumably reducing their risk of cancer. HCC survival rates remain universally poor, but early detection and treatment in developed countries has improved survival in selected patients. Despite these advances, worldwide HCC rates remain high, and additional preventive efforts are needed. The most important opportunity is wider distribution of hepatitis B virus vaccine in endemic areas. Development of an HCV vaccine, improved antiviral therapies, and better methods for HCC detection would also help decrease morbidity and mortality from HCC. HCC prevention efforts provide a paradigm for preventive oncology in cancers of viral etiology.