In order to assess the association between antibodies to hepatitis C virus (anti-HCV) and hepatocellular carcinoma (HCC), as well as the interaction of anti-HCV with other HCC risk factors in Taiwan, a total of 127 pairs of newly diagnosed HCC patients and healthy community controls were studied. Case-control pairs were individually matched for age (+/- 3 years), sex, residence, and ethnicity. Serum samples from study subjects were examined for anti-HCV by enzyme immunoassays as well as hepatitis B surface antigen (HBsAg) and e antigen (HBeAg) by radioimmunoassays using commercial kits. The habits of cigarette smoking, alcohol drinking, and peanut consumption were obtained through standardized interviews according to a structured questionnaire. Both the anti-HCV as well as the carrier status of HBsAg and HBeAg were significantly associated with HCC showing a multivariate-adjusted odds ratio of 24.8 for carriers of HBsAg alone, 33.5 for carriers of both HBsAg and HBeAg, and 23.7 for those who were positive for anti-HCV. The population-attributable risk percentage was estimated as 3% for anti-HCV alone, 69% for HBsAg carrier status alone, and 6% for both anti-HCV and HBsAg in Taiwan. There were also synergistic effects on HCC development for anti-HCV with HBsAg carrier status, cigarette smoking, and habitual alcohol drinking.