There is an excess prevalence of markers of active infection with hepatitis B virus in patients with primary liver cancer in many parts of the world. Early age of infection with hepatitis B virus is likely to be an important factor, resulting in persistent infection that may progress to chronic liver damage. Results of recent experimental studies are consistent with integration of hepatitis B viral DNA with host cell DNA molecules. It is likely that primary liver cancer is the cumulative result of several cofactors including infection with hepatitis B virus; genetic, immunologic, hormonal, and nutritional factors; and environmental factors including mycotoxins and chemical carcinogens.