During the past 30 years, hepatocellular carcinoma (HCC) in Japan has kept linearly increasing from 10 to 30 per 100,000 population per year and is expected to grow further. The increment is attributed to infection with hepatitis C virus (HCV). Hence, there is a pressing need to find subjects with persistent HCV infection in the general population of Japan and take necessary measures to prevent HCC developing in them. As a first approach toward this goal, the sex- and age-specific prevalence of ongoing HCV infection was surveyed in 3,485,648 first-time blood donors during 1995-2000. Taking into account the size of subpopulations with different sex and age in Japan registered at the Census 2000, there are an estimated 884,954 HCV carriers aged from 16 to 69 years, and 759,316 (86%) of them are older than 40 years, with an increased risk for HCC; they are hidden in the society, without overt liver disease. The national 5-year project searching for HCV carriers in the general population was started in April 2002. Subjects are examinees of health check-ups, which they receive every 5 years when reaching the age of 40, as well as those at increased risk for HCV infection. The project detected HCV RNA in 14,672 of the 1,298,746 (1.1%) health check examinees and in 16,721 of the 624,734 (2.7%) high-risk individuals during the first fiscal year. Subjects found with HCV RNA have been referred to clinics and hospitals with expert hepatologists. Hopefully, this project will decrease HCC development in HCV carriers in Japan and be considered in other countries where increases in HCC are predicted from the current age-specific prevalence of anti-HCV. Copyright (C) 2006 S. Karger AG, Basel.