The human melanoma antigen (MAGE) gene family encode tumor-specific antigens recognized by autologous cytotoxic T lymphocytes. Some of these antigens may be potentially useful for cancer-specific immunotherapy. The expression of MAGE genes has been reported not only in melanoma but also in various other malignant tumors. However, little is known about the expression of these genes in human hepatocellular carcinoma (HCC). We therefore analyzed, by means of a reverse transcription-polymerase chain reaction (RT-PCR), the expression of MAGE-1, MAGE-2, and MAGE-3 genes in 60 tissue samples resected from HCCs. The MAGE-1, MAGE-2, and MAGE-3 genes were expressed in 18 (30.0%), 9 (15.0%), and 15 (25.0%), respectively, of the 60 tumor-tissue samples. Nineteen (31.7%) samples expressed at least one of the three MAGE genes, and 8 (13.3%) expressed all three genes. In contrast, none of the MAGE genes was expressed in any of the 60 adjacent non-tumorous liver samples. The age of patients was significantly older in at least one MAGE-positive group (MAGE-positive groups) than in the MAGE-negative ones (p<0.05). The tumor size was significantly larger in MAGE-positive groups than in the negative ones (p<0.05). The serum alpha-fetoprotein level was significantly lower in MAGE-positive groups than in negative ones (p<0.05). Patients with tumors expressing at least one MAGE gene showed a better recurrence-free survival rate than those with tumors showing no MAGE gene expression (p<0.05). These results indicated that the MAGE genes were exclusively expressed in cancerous tissues of a considerable proportion of patients affected by HCC, and that some of these patients might be potential candidates for tumor-specific immunotherapy using the MAGE encoded antigens.