Objective To investigate the expression of cyclooxgenase 2 (COX-2) and vascular endothelial growth factor (VEGF) in clear cell renal cell carcinoma (CCRCC) and their correlation with Prognosis. Methods EnVision immunohistochemistry was used to determine the expression of COX-2 and VEGF in 80 CCRCC tissues and 20 normal kidney tissues .The relationship between the above marks and prognosis were analyzed. Results The positive rates of COX-2[65.00 % (52/80) vs 10.00 % (2/20), x2= 7.760, P= 0.021]and VEGF[61.25 % (49/20) vs 20.00 (4/80),x2 = 8.870, P= 0.012]were much higher in CCRCC than those in normal kidney. The expression of COX-2 was correlated with TNM stage (x2 = 8.200,P =0.005), histological grade (x2 = 13.860, P = 0.000) and lymph node metastasis (x2 = 6.050, P = 0.001) in CCRCC, but not with age (x2 = 0.560, P = 0.663) and diameter of tumor (x2 = 0.700, P = 0.528). Both COX-2 expression and VEGF expression were associated significantly with prognosis in CCRCC (x2 = 18.280,P = 0.038;x2 = 6.420, P= 0.042, respectively). There was a positive correlation between COX-2 and VEGF in CCRCC (r =0.485, P < 0.01). Conclusion COX-2 is related to prognosis in CCRCC and can be used as prognostic indicators in patients.