Abstract: To study the expression of COX-2 and survivin in esophageal squamous cell carcinoma (ESCC), and their prognostic significance. Methods The expression of COX-2 and survivin in 56 cases of ESCC sections was detected by immunohistochemistry with Envision non-biotin detection system and tissue micro-array (TMA). Cox proportional hazard regression model was performed to study the relationship between their expression and patients' prognosis. Results The positive rate of COX-2 and survivin was 69.6%(39/56) and 71.4%(40/56), respectively. COX-2 expression was positive correlation with survivin expression (P=0.002,r=0.614). The both COX-2 and survivin were correlated with tumor infiltration depth, lymph node metastasis and TNM staging. The median survival of COX-2 or survivin positive group was significant shorter than that of COX-2 (25.13 vs. 69.33,P=0.0001)or survivin negative group (25.23 vs. 69.32,P=0.0000),respectively， Cox regression multivariate survival analysis indicated the expression of COX-2 and survivin proteins were the independent prognostic factors for ESCC patients. Conclusion This study showed that the expression of COX-2 and survivin was up-regulated in ESCC. COX-2 expression was positive correlation with survivin expression, which indicated that both proteins might play a synergetic role during ESCC progression. The over-expression of COX-2 and survivin proteins was the independent prognostic factors for ESCC patients.