This community-based prospective study examined the effects of viral infections and lifestyle habits on hepatocellular carcinoma (HCC) risk in Japan. A baseline survey was conducted for 981 males and 2,078 females in June 1992 and evaluated hepatitis B surface antigen, second-generation hepatitis C virus antibody, and history of cigarette smoking and habitual alcohol consumption. By March 1997, 14 males and 8 females had been newly diagnosed with HCC. After controlling for gender and age by using the Cox model, the authors found that positivity for hepatitis B surface antigen (hazard ratio = 7.28, 95% confidence interval: 1.62, 32.61; p < 0.01) and positivity for high-titer hepatitis C virus antibody (hazard ratio = 40.38, 95% confidence interval: 11.71, 139.21; p < 0.001) were significantly associated with HCC risk, although a history of smoking or alcohol consumption was not significantly related to risk. There was a significant interaction on an additive scale for the risk of HCC development between high-titer hepatitis C virus antibody status and a history of smoking (p < 0.05) in spite of no significant interaction on a multiplicative scale. Although preventing the transmission of hepatitis viruses is most important for reducing the risk of HCC, intervention regarding lifestyle habits such as cigarette smoking should not go unheeded.