Mortality rates from liver cancer among Koreans living in Osaka are 2–3 times higher than those among Japanese. Our previous study revealed that chronic hepatitis B virus (HBV) infection and excessive alcohol drinking are two major risk factors for hepatocellular carcinoma (HCC) among Koreans in Osaka, although more than 70% of the HCC cases were negative for hepatitis B surface antigen (HBsAg). Using a recently developed immunoassay for detecting serum hepatitis C virus antibody (HCV-Ab), the role of HCV infection was evaluated in a case-control study. The case group consisted of 90 Korean patients who were admitted to Kyowa Hospital in Osaka, and were newly diagnosed as HCC during the period from January 1989 to December 1992. The control group consisted of 249 Korean patients admitted to Kyowa Hospital during the same period and matched in age groups to the HCC cases. Seventy-four and 16.7% of cases were positive for HCV-Ab and HBsAg, respectively. Besides, 41.1% of cases were heavy drinkers. Multiple logistic regression analysis revealed that the adjusted relative risk was 92.4 for HCV-Ab positive and 58.2 for HBsAg positive, as compared with both HCV-Ab and HBsAg negative. Elevated risk was also demonstrated for males with a history of heavy drinking. There was no significant association between the risk of HCC and a history of blood transfusion or cigarette smoking. It was concluded that chronic HCV infection plays a major role in the etiology of HCC among Koreans living in Osaka, in addition to HBV and heavy drinking.