To elucidate the appearance rates of hepatocellular carcinoma in cirrhosis and to assess the risk factors for hepatocellular carcinogenesis, we prospectively studied 795 consecutive patients with viral or alcoholic cirrhosis for 2 to 17 yr (median of 5.8 yr). During the observation period, hepatocellular carcinoma developed in 221 patients. Cumulative appearance rates of hepatocellular carcinoma were 19.4%, 44.3% and 58.2% at the end of the fifth, tenth and fifteenth years, respectively. When classified by the type of hepatitis virus infection, the appearance rates of hepatocellular carcinoma in 180 patients with only HBsAg and in 349 patients with only antibodies to hepatitis C virus were 14.2% and 21.5% at the fifth yr, 27.2% and 53.2% at the tenth yr and 27.2% and 75.2% at the fifteenth yr, respectively. Cox proportional hazard model identified that alpha-fetoprotein levels (p = 0.00001), age (p = 0.00067), positive hepatitis C virus antibodies (p = 0.00135), total alcohol intake (p = 0.00455) and indocyanine green retention rate (p = 0.04491) were independently associated with the appearance rates of hepatocellular carcinoma. Whereas age and indocyanine green retention rate were independent predictors for the appearance rate of liver tumor in the subgroup of HBsAg-positive patients, alpha-fetoprotein levels, age and past alcohol consumption were independent predictors in the group of hepatitis C virus antibody-positive patients. These epidemiological results suggest that some differences exist in the activity and modes of cancer promotion between hepatitis B virus infection and hepatitis C virus infection.