Primary liver cancer, 95% of which is hepatocellular carcinoma (HCC), has ranked third in men and fifth in women as a cause of death from malignant neoplasm in Japan. Although the number of deaths and death rates from HCC increased until 2002 in Japan, annual deaths (34 089) and the death rate (27.0/100 000) from liver cancer decreased in 2003. Hepatitis C virus (HCV)-related HCC represents 75% of all HCC in Japan. The incidence of HCC without hepatitis B surface antigen (HBsAg) or anti-HCV accounted for 7–12% of HCC in Japan andhalf of non-B non-C-HCC was of unknown origin. Geographically, HCC is more frequent in western than eastern Japan, and the death rates from HCC in each prefecture correlate with the prevalence of anti-HCV, but not with HBsAg prevalence. Interferon therapy for chronic hepatitis C has reduced the risk factors for development of HCC, especially among patients with sustained response.