Abstract: To investigate the expression of Wnt2,β-catenin and their target genes such as c-myc,cyclinD1 in tissues of esophageal squamous cell carcinoma (ESCC). Methods The expression level of Wnt2,β-catenin,c-myc, cyclin D1 in 40 cases of esophageal squamous cell carcinoma was detected by immunohistochemistry,and its correlation with clinicopathological features was analyzed. Results The aberrant expressions of Wnt2,β-catenin,c-myc and cyclinD1 in ESCC was higher than tissue adjacent to cancer and normal tissues, there was a significant difference among the groups（P<0.01）. The expressions of β-catenin and c-myc protein were closely correlated with infiltrative depth and lymphatic metastasis in esophageal squamous cell carcinoma ESCC(P<0.05). Conclusion Wnt2β-catenin Tcf4 signal pathway plays an important role in ESCC and may become a prognostic factors or gene therapy target for ESCC.