Objective To investigate whether N-cadherin modulates expression of β-catenin and activation of the Wnt signaling pathway in hepatocellular carcinoma ( HCC ). MethodsThe expressions of N-cadherin and β-catenin in 64 HCC tissues were measured by immunohistochemistry and the relationship between them was studied. Furthermore, N-cadherin expression in HCC cell lines, HCCLM3 and SMMC-7721 cells, was regulated and its effect on expression of β-catenin and activity of Wnt singnaling pathway was evaluated. Results Among the 64 HCCs examined,34 HCCs showed reduced N-cadherin expression; β-catenin staining was observed on cell membranes but not in cell nuclei and 13 HCCs showed reduced membranous staining;the reduced expression of β-catenin on cell membranes was correlated with reduced N-cadherin expression(P < 0. 05 ). Down-regulation of N-cadherin in HCCLM3 cells resulted in reduced membranous β-catenin expression but not activation of the Wnt signaling pathway. In contrast, up-regulation of N-cadherin expression in SMMC-7721 cells led to increased expression of membranous β-catenin but had no effect on Wnt signaling pathway. Conclusion In HCC,the level of N-cadherin was positively correlated with membranous β-catenin expression:however, N-cadherin was not involved in regulation of the Wnt signaling pathway. Key words: Carcinoma,hepatocellular; N-cadherin; β-catenin; Wnt signal pathway