Abstract: Objective To investigate the impact of PCNA, p53 and Nm23 expression and adjuvant radiotherapy on the prognosis of locally advanced thoracic esophageal squamous cell carcinoma patients after operation. Methods From March 2005 to December 2009, 222 patients with locally advanced thoracic esophageal carcinoma received radical esophagectomy in the Third Affiliated Hospital of Soochow University. We analyzed the correlation between the expression of PCNA, p53, Nm23 and clinicopathological factors as well as recurrence, metastasis. Kaplan-Meier method was used to calculate the survival rates. Log-rank and Cox proportional model were used to analyze the impact of PCNA, p53 and Nm23 expression and adjuvant radiotherapy on the prognosis of locally advanced thoracic esophageal squamous cell carcinoma patients after operation. Results The expression of PCNA and p53 were closely correlated with tumor differentiation. The expression of Nm23 had no obvious correlation with clinicopathological factors. PCNA and p53 expression, tumor stage and adjuvant radiotherapy were the significant factors for local recurrence or distant metastasis after operation. Univariate and multivariate analysis showed that PCNA and p53 expression, tumor differentiation, TMN stage and adjuvant radiotherapy were the independent prognostic factors for the OS of the patients after radical esophagectomy. Conclusion PCNA and p53 expression, not Nm23, are the key biologic predictive factors for the survival of locally advanced thoracic esophageal carcinoma patients after operation. Advanced thoracic esophageal squamous cell carcinoma patients with the negative expression of PCNA and p53 will benefit more from postoperative adjuvant radiotherapy.