To assess the interaction of alcohol, hepatitis C virus (HCV), and hepatitis B virus (HBV) infection in hepatocarcinogenesis, we prospectively observed 449 patients with liver cirrhosis (LC) who presented to our outpatient clinics in 1 month; 164 patients with habitual drinking [alcoholic liver-liver cirrhosis (AL-LC)] who had taken > 72 g alcohol/day (HCV-positive 81 cases: HCV + AL; HCV-negative 83 cases: AL); 176 patients with HCV infection, but without alcohol intake: 34 patients with HBV infection: 6 patients with HCV and HBV coinfection; and 82 patients with liver diseases from other etiologies, such as primary biliary cirrhosis. In the HCV group, the cumulative occurrence rate of hepatocellular carcinoma (HCC) was 9%, 18%, and 23% in the first, second, and third years, respectively. In the HCV + AL group, that was 13%, 17%, and 28%, respectively. There was no difference in the HCC occurrence rate between the two groups. In the AL group, the cumulative HCC occurrence rate was only 1% during the observation period of 3 years. The occurrence rate was significantly lower in the AL group, compared with the HCV and the HCV + AL groups. In the HBV group, the cumulative occurrence rate of HCC during the observation period of 3 years was 17%, which was similar to that of the HBV + AL group, 14%. We also examined some other variables that might be related to the development of HCC. The cumulative occurrence rate of HCC in male patients was 31%, whereas that was 18% in female patients. In the HCV group, there was a significant increase of HCC occurrence rate in male patients. In contrast, no difference was observed in the HCC occurrence rate between male and female patients in the HBV group. The present study suggests that alcohol alone may not be an independent risk factor for HCC, nor does it accelerate HCC development in LC patients with HCV and HBV infection during the prospective observation of 3 years.