We conducted a hospital-based case-control study to investigate the effects of alcohol drinking on hepatocellular carcinoma (HCC) among patients with hepatitis C virus (HCV) infection, with special reference to the disease course and changes in drinking habits. From among 1159 HCV-RNA positive patients under clinical follow-up at Osaka City University Hospital (OCUH), we identified 73 cases newly diagnosed with HCC during the past 3 years and selected 253 matched controls without HCC. The odds ratios were calculated for cumulative and average daily ethanol consumption, during three different periods (lifetime, before, and after the first identification of liver disease), using a logistic regression model. Among all subjects, there was a trend towards an inverse association between HCC and lifetime ethanol consumption (P=0.059-0.066). The tendency was similar for ethanol consumption before the first identification of liver disease, while no associative trend was indicated after the first identification. Among those with minor changes on abdominal ultrasonography findings at the first OCUH visit, a positive association was suggested for ethanol intake after the first identification, although results were not statistically significant. In conclusion, our results did not demonstrate a strong positive association between alcohol drinking and HCV-related HCC in this population.