Objective To investigate the expression of Cripto-1 in esophageal carcinoma and its relationship with epithelial-mesenchymal transformation (EMT). Methods RT-PCR and Western blotting were used to examine the expression levels of Cripto-1 in carcinoma, paraneoplastic and normal esophageal mucosa tissue of 41 patients with esophageal carcinoma. The protein expressions of Cripto-1 and EMT markers such as N-cadherin, Vimentin and E-cadherin were detected by immunohistochemistry, and the clinical pathologic parameters were simultaneously analyzed. The correlation between Cripto-1 and the expression of N-cadherin, Vimentin and E-cadherin were also analyzed. Results The expression levels of Cripto-1 mRNA and protein were significantly higher in esophageal carcinoma (0.35±0.08 and 0.62±0.06) than in paraneoplastic (0.22±0.04 and 0.45±0.07) and normal esophageal mucosa tissue (0.13±0.03 and 0.33±0.05, P<0.05). Immunohistochemistry revealed that the positive expression rates of Cripto-1, N-cadherin, Vimentin and E-cadherin protein in esophageal carcinoma were 53.7%, 51.2%, 61.0% and 36.6% respectively. The expression of Cripto-1 showed a positive correlation with N-cadherin (r=0.463, P<0.05) and Vimentin (r=0.460, P<0.05), while a negative correlation with E-cadherin (r=－0.310, P<0.05) was found. The expression of Cripto-1 also showed a significant correlation with lymph node metastasis, distant metastasis and clinical stage (P<0.05). Conclusion The expression of Cripto-1 is closely related to the carcinogenesis and development of esophageal carcinoma, and may promote the invasion and metastasis of esophageal carcinoma by regulation of EMT.