Snail is a zinc-finger transcription factor that triggers the epithelial-mesenchymal transition (EMT) by directly repressing E-cadherin expression. However, the relationship between E-cadherin and Snail expression remains unclear in esophageal squamous cell carcinoma (ESCC). The purpose of the present study was to evaluate the clinical significance of E-cadherin and Snail expression in ESCC. Immunohistochemistry was used to investigate the expression of E-cadherin and Snail proteins in 194 patients with ESCC. The relationship between expression of these proteins and clinicopathological factors was analyzed, and the usefulness of Snail in disease prognosis was evaluated in relation to E-cadherin expression. E-cadherin expression was preserved in 41.2% of tumors, and Snail expression was confirmed in 61.7%. Tumors with reduced E-cadherin expression invaded deeper (P<0.0001), had more lymph node metastasis (P<0.0001) and had more lymphatic invasion (P=0.0011) than tumors with preserved expression. Tumors that were positive for Snail expression invaded deeper (P=0.0385), had more distant lymph node metastasis (pM) (P=0.0051) and had a more advanced stage (P=0.0044) than those that were negative for Snail expression. Snail expression was not significantly correlated with reduced E-cadherin expression. Patients with reduced E-cadherin expression or positive Snail expression had poor clinical outcomes. In the preserved E-cadherin group, overall survival rate was better in patients with negative Snail expression than in those with positive Snail expression (P=0.035). Snail appears to play a key role in preserved E-cadherin expression. Further studies on other molecules in the pathways related to reduced E-cadherin expression in ESCC from the view-point of EMT are necessary.