Background & Aims: Hepatitis C virus (HCV) infection usually induces chronic hepatic inflammation, which favors the initiation and progression of hepatocellular carcinoma.Moreover, rmicroRNA-155 (miR-155) plays an important role in regulating both inflammation and tumorigenesis.However, little is known about whether and how miR-155 provides the link between inflammation and cancer.Methods & Results: In this study, we found that miR-155 levels were markedly increased in patients infected with HCV.miR-155 transcription was regulated by NF-κB, and p300 increased NF-κB-dependent miR-155 expression.The overexpression of miR-155 significantly inhibited hepatocyte apoptosis and promoted cell proliferation, whereas miR-155 inhibition induced G0/G 1 arrest.Upregulated miR-155 resulted in nuclear accumulation of β-catenin and a concomitant increase in cyclin D1, c-myc and survivin.Gain-of-function and loss-of-function studies demonstrated that miR-155 promoted hepatocyte proliferation and tumorigenesis by increasing Wnt signaling in vitro and in vivo, and DKK1 (Writ pathway inhibitor) overexpression inhibited the biological role of miR-155 in hepatocytes.Finally,adenomatous polyposis coli (APC), which negatively regulates Wnt signaling, was identified as the direct and functional target of miR-155.Conclusion: HCV-induced miR-155 expression promotes hepatocyte proliferation and tumorigenesis by activating Wnt signaling.The present study provides a better understanding of the relationship between inflammation and tumorigenesis, and thus may be helpful in the development of effective diagnosis and treatment strategies against HCV-HCC.