Liver cancer is one of the leading causes of cancer deaths in Asia and Africa. The epidemiology of liver cancer is distinctive in Japan, where chronic infection with hepatitis C virus (HCV) rather than hepatitis B virus (HBV) plays the major role in the etiology. In this paper, together with a brief review of the descriptive epidemiology of liver cancer and its prevention, Japanese experiences of liver cancer occurrence and some epidemiological studies are described, and Japanese national projects directed against hepatitis and liver cancer are presented. Distinctive time-trends have been observed for liver cancer incidence in Japan. The rates for over 55-59 year olds (both sexes) showed a peak in the birth cohort of 1931-1935, while the rates for less than 50-54 year old females indicate a decreasing trend. The extremely high incidences among birth cohorts around 1931-1935 seems to be related to endemic HCV infection in this generation in Japan. Follow-up studies not only of patients with chronic hepatitis C but also of apparently healthy carriers of HCV showed an increased risk of hepatocellular carcinoma (HCC). Cumulative risk of HCC (40-74 years of age) was estimated as reaching 21.6% (males) and 8.7% (females) among anti-HCV positive voluntary blood donors. Retrospective cohort studies indicated interferon (IFN), with or without ribavirin, to be effective for reducing the risk of HCC among patients with chronic hepatitis C. Periodic examination with ultrasonography and measurement of alpha-fetoprotein has become common practice for early detection of HCCs among patients with chronic hepatitis or liver cirrhosis in Japan. A non-randomized controlled study was conducted to evaluate the effect of periodic examination on mortality, but we failed to show any beneficial effects of screening for liver cancer. In the fiscal year 2002, Japanese National Projects directed against hepatitis and HCC were started, in which blood tests for HCV and HBsAg are offered just once at the age of 40, 45, 50, 55, 60, 65 or 70 for five years. Participants are categorized as either HCV carriers or non-carriers. HCV carriers are further examined by liver disease specialists, seeking indications for IFN therapy. Type C chronic hepatitis patients are recommended to receive IFN therapy with or without ribavirin. This project is expected to become a model of liver cancer control in HCV-endemic countries. Recently however, the US Preventive Service Task Force has recommended against routine screening for HCV infection in asymptomatic adults in the general population who are not at increased risk of infection. This divergence of views is also discussed.