A total of 71 consecutive patients with unresectable hepatocellular carcinoma were analyzed retrospectively to determine the significant prognostic factors. All the patients received systemic chemotherapy in a phase 2 study from 1980 to 1990, with no other anticancer treatment. Median survival time and 1-yr and 2-yr survival rates were 5.6 mo, 23% and 5%, respectively. By the univariate analysis, a performance status of 0-1 and tumor size less than 50% of the liver cross-sectional area were shown to be the factors most significantly favoring a better prognosis. By the multivariate analysis using the Cox proportional hazards model, a performance status of 0-1 (p less than 0.001), absence of tumor thrombus in the main portal trunk (p = 0.003) and age less than 60 yr (p = 0.036) were independent favorable prognostic factors. A prognostic index was calculated from these three factors according to the following equation: 1.8109 x (0 = performance status of 0-1 and 1 = performance status of 2-3) + 0.9322 x (0 = tumor thrombus absent in the main portal trunk and 1 = present) + 0.6996 x (0 = age less than 60 yr and 1 = age greater than or equal to 60 yr). This index was used to classify the patients into three groups with a good, intermediate and poor prognosis. The median survival times for these three groups were 9.8, 3.8 and 1.9 mo, respectively (p less than 0.01). The results of this study may be useful in the design and analysis of future clinical trials of systemic therapy for hepatocellular carcinoma.