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 present 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.