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The clinical outcome of cirrhotic patients with hepatocellular carcinoma (HCC) depends both on the residual liver function and tumor characteristics. However, the relative prognostic weight of these variables is not well defined. The aims of this study were to verify the value of known prognostic factors and to devise a prognostic index more sensitive than the commonly used Okuda stage. A retrospective analysis of the cases of HCC diagnosed at 16 Italian institutions from 1990 to 1992 was performed. Overall survival was the only end point used in the analysis. The Cox model, stratified by locoregional treatment, was used for multivariate analyses. The final model was derived from 10 randomly chosen training samples, and the prognostic validity of the Cancer of the Liver Italian Program (CLIP) score was assessed on the corresponding testing samples. Four hundred thirty-five cases of HCC were collected. As of January 1997, 313 patients (72%) were deceased. Overall median survival was 20 months. At multivariate analysis, independent predictive factors of survival were Child-Pugh stage, tumor morphology, alpha-fetoprotein (AFP), and portal vein thrombosis. A simple scoring system (CLIP score) was thus produced, assigning linear scores (0/1/2) to the covariates. Compared with Okuda stage, the CLIP score, structured as a six-category tool, has a greater discriminant ability, revealing a class of patients with an impressively more favorable prognosis and another class with a relatively shorter life expectancy. The CLIP score is a new prognostic system that accounts for both liver function and tumor characteristics. It is easy to calculate and appears to give more precise information than the Okuda stage.