AIM: To identify biomarkers indicating virus-specific hepatocarcinogenic process,differential mRNA expres-sion in 32 patients with hepatitis B virus (HBV)-/hepa-titis C virus (HCV)-associated hepatocellular carcinoma (HCC) were investigated by means of cDNA microar-rays comprising of 886 genes. METHODS: Thirty two HCC patients were divided into two groups based on viral markers: hepatitis B virus positive and HCV positive. The expression profiles of 32 pairs of specimens (tumorous and surrounding non-tumorous liver tissues),consisting of 886 genes were analyzed. RESULTS: Seven up-regulated genes in HBV-associat-ed HCC comprised genes involved in protein synthesis (RPS5 ),cytoskeletal organization (KRT8 ),apoptosis related genes (CFLAR),transport (ATP5F1),cell mem-brane receptor related genes (IGFBP2),signal trans-duction or transcription related genes (MAP3K5),and metastasis-related genes (MMP9). The up-regulated genes in HCV-infected group included 4 genes: VIM (cell structure),ACTB (cell structure),GAPD (glycolysis) and CD58 (cell adhesion). The expression patterns of the 11 genes,identified by cDNA microarray,were con-firmed by quantitative RT-PCR in 32 specimens. CONCLUSION: The patterns of all identified genes were classified based on the viral factor involved in HBV-and HCV-associated HCC. Our results strongly suggest that the pattern of gene expression in HCC is closely associated with the etiologic factor. The pres-ent study indicates that HBV and HCV cause hepato-carcinogenesis by different mechanisms,and provide novel tools for the diagnosis and treatment of HBV-and HCV-associated HCC.