The transcription factor Twist plays a key role in cancer metastasis. The present study aimed at investigating clinical Twist expression in patients with esophageal squamous cell carcinoma (ESCC) in order to correlate the Twist levels with the patients’ survival rates and their other clinical parameters. Immunohistochemical staining using polyclonal Twist antibody was performed on paraffin embedded specimens of 112 ESCC patients and non-neoplastic esophageal epithelium used as a control. The overall staining intensity was analyzed along with clinicopathologic data and prognosis of ESCC. Twist expression was significantly higher in ESCC than in non-neoplastic oesophageal epithelium (P < 0.001). The Twist expression directly correlated with distant metastasis after esophagectomy (P = 0.001). Kaplan–Meier estimate in conjunction with the log-rank test revealed an inverse proportion relationship between postoperative survival rates of the patients and their Twist expression levels (log-rank, P < 0.001). In addition, Cox mono-variate analysis revealed that T/N classification, pTNM stage, distant metastasis and Twist expression were significantly correlated with mortality risk of patients after operation (P < 0.05). By Cox multi-variate analysis, Twist expression (risk ratio = 2.394; P < 0.001) and N classification were identified as the independent prognostic factors of patient survival. In conclusion, upregulated Twist expression in the primary ESCC significantly correlates with the high risk of subsequent development of distant metastasis and low postoperative survival rates; the latter was not significantly correlated with patients’ age, gender, tumor location and differentiation. Twist may serve as an independent prognostic marker for predicting development of distant metastasis in ESCC patients and their survival.