Aims: Our study investigates the significance of the expression of Wnt pathway proteins including β-catenin, Axin, β-transducin-repeat- containing protein (β-TrCP), and adenomatous polyposis coli (APC) in squamous cell carcinoma of the esophagus (ESCC). Methods: Immunohistochemical analysis was performed on paraffin-embedded tissue specimens from 128 resected ESCC tumors to detect the expression of β-catenin, Axin, β-TrCP, and APC. Correlation between immunoexpression, clinicopathological parameters, and patient survival was analyzed. Results: Increased β-catenin expression was noted in 22 (18.2%) of 121 tumor specimens. Reduced expression of Axin, β-TrCP, and APC was observed in 57 (46.0%) of 124, 29 (24.4%) of 119, and 54 (48.2%) of 119 specimens, respectively. No correlation was found among these protein expressions. Axin protein expression was inversely correlated with tumor invasion depth (P = 0.033). Reduced Axin protein expression, lymph node involvement, and distant metastasis were significant negative predictors for overall survival and disease-free survival on univariate analysis. In multivariate analysis, reduced Axin expression remained a significant prognostic factor for patients with ESCC (P = 0.005). Conclusions: Reduced Axin expression was observed in 46% of ESCC tumor specimens and was associated with poor prognosis in patients with ESCC. Further study is mandatory to elucidate the underlying mechanism responsible for loss of Axin expression and the role of Axin in ESCC tumorigenesis.