Several studies have reported the role of coffee for hepatocellular carcinoma (HCC). However, no study investigated about the relation of coffee for HCC among individuals with a relevant risk factor, i.e., hepatitis C virus (HCV) infection. Thus, we conducted a hospital-based case-control study to assess an association between coffee and HCC, in which both 73 cases and 253 controls were patients with chronic type C liver disease. To consider potential changes in coffee intake due to progression of liver disease, the effect of coffee was estimated separately before and after first identification of liver disease. Odds ratios (OR) and 95% confidence intervals (CI) for HCC risk were calculated using the conditional logistic regression model. Coffee drinking on a daily basis (>/=1cup/day) revealed lowered ORs as compared with non-drinkers both before first identification of liver disease (OR 0.38; 95% CI: 0.13-1.12; P=0.078) as well as thereafter (OR 0.19; 95% CI: 0.05-0.71; P=0.032). Even after excluding subjects who reported a reduction in the frequency of coffee intake after first identification of liver disease, this negative correlation persisted (OR 0.35; 95% CI: 0.12-1.06; P=0.063). Taken together, coffee may be a protective factor for HCC among those infected with HCV.