The present study analyzed the polymorphisms of apoptosis-related genes and their impact on the response to chemotherapy and survival of patients with colorectal cancer.A total of 76 patients with recurrent or metastatic colorectal cancer treated with capecitabine and oxaliplatin (XELOX) combination chemotherapy were enrolled in the present study. The single nucleotide polymorphisms of 15 apoptosis-related genes (TP53, BCL2L, TNFRSF10B, AKT1, PTGS2/COX2, BID, RIPK1, FAS, FASL, caspase 3, and caspase 6-10) were determined using a PCR-RFLP assay.No significant association between the polymorphisms and the response was found for any of the genes analyzed. However, the T/T genotype of PTGS2 8473T>C (rs5275) was significantly correlated with a better progression-free survival (PFS) and overall survival (OS) when compared to the combined T/C and C/C genotype (Hazard ratio [HR] = 0.47; P value = 0.046 and HR = 0.16; P = 0.013, respectively) in a multivariate analysis adjusted for age, sex, performance status, disease status and curative resection. No association was noted between the other polymorphisms and survival.The PTGS2 8473T>C polymorphism was found to be correlated with PFS and OS in patients with advanced colorectal cancer treated with XELOX chemotherapy.