To investigate whether hepatitis B virus (HBV) and hepatitis C virus (HCV) infection are risk factors for liver cirrhosis and hepatocellular carcinoma (HCC), a case-control study of 102 cirrhotic HCC patients, 102 sex-matched and age-matched patients with liver cirrhosis, and 102 matched patients with non-hepatic disease controls was performed. The prevalences of hepatitis B surface antigen (HBsAg) and antibody to HCV (anti-HCV) in HCC (70.5%, 39.2%) and liver cirrhosis (74.5%, 27.4%) were higher than controls (16.6%, 10.5%) (P = 0.0001). In HBsAg-negative patients, the prevalence of anti-HCV in cirrhotic HCC (66.6%) and liver cirrhosis (46.1%) was higher than in controls (10.5%; P = 0.0001). There was no such difference in HBsAg-positive patients. Multivariate analysis revealed that both HBsAg and anti-HCV were important risk factors for HCC (odds ratio, 6.52 and 4.59, respectively) and liver cirrhosis (odds ratio, 4.22 and 2.29, respectively). There was no difference in odds ratio when HCC and liver cirrhosis were compared. Our result implies that both HBV and HCV are independent risk factors for cirrhotic HCC and liver cirrhosis in Taiwan.