Fas antigen belongs to the tumor necrosis factor receptor family and is known to induce apoptosis. This protein is abundantly expressed in hepatocytes, especially in acute and chronic hepatitis. To elucidate the clinical significance of Fas in hepatocellular carcinoma (HCC), we investigated its expression in 50 HCC having various characteristics. Fas was comprehensively expressed in non-cancerous hepatocytes as well as bile ducts. It was moderately expressed in histiocytes in the stroma rather than in infiltrating lymphocytes. In HCC, Fas expression was significantly reduced when there was poor differentiation (p<0.001), portal tumor thrombus and extracapsular invasion (p<0.05) according to univariate analysis. Multivariate analysis revealed statistical significance between Fas expression and the degree of differentiation (p=0.0002). These results suggest that HCC, like non-cancerous hepatocytes, express Fas antigen, when they are well or moderately differentiated but lose this ability when they become poorly differentiated as the carcinoma advances.