AIM: Nucleotide excision repair was a complex biochemical process that involved in the repair of many kinds of DNA damage. Previous study suggested that xeroderma pigmentosum group C (XPC) gene played an important role in the process of DNA damage repair. This study aimed to explore the influence of XPC gene  polymorphism on the prognosis of patients with colorectal cancer (CRC) who were treated with capecitabine-related adjuvant chemotherapy. METHODS: A total of 158 patients with CRC who received surgical resection and capecitabine-based adjuvant chemotherapy were included in this study consecutively. Baseline clinical characteristics of patients were collected and analyzed. Additionally, peripheral blood specimens of the patients were collected for polymorphism analysis of XPC gene and mRNA expression of XPC, respectively. The association analysis between XPC polymorphism and prognosis and mRNA expression was performed. Cox regression analysis was used for multivariate adjustment. RESULTS: Prognostic data in the 158 patients with CRC who received capecitabine-based adjuvant chemotherapy was collected retrospectively. The median follow-up duration of the patients was 5.0 years (range: 0.25-7.5 years). The median DFS and OS of the 158 patients with CRC was 4.5 years and 5.7 years, respectively. XPC polymorphism analysis suggested that rs2228001 was of clinical signifi- cance. The prevalence of rs2228001 polymorphism among CRC patients was: TT genotype 86 cases (54.4%), TG genotype 60 cases (38.0%) and GG genotype 12 cases (7.6%), resulting in a minor allele frequency of 0.27, which was in accordance with Hardy-Weinberg equilibrium (P=0.733). TG and GG genotypes were merged in the subsequent analysis. The prognostic results exhibited that the median DFS of patients with TT genotype and TG/GG genotype was 4.5 and 5.7 years, respectively (?2= 7.072, P=0.008). Furthermore, the median OS of the two genotypes were 5.0 and 5.9 years (?2= 5.416, P=0.020). Additionally, analysis of XPC gene mRNA expression in 65 specimens suggested that the mRNA expression of XPC in PBMC of the patients with TG/GG genotypes were significantly higher than that of the patients with TT genotype (t=6.478, P<0.001). CCONCLUSION: Polymorphism of rs2228001 in XPC gene was associated with prognosis of patients with CRC who received capecitabine-based adjuvant chemotherapy. And the conclusion should be confirmed in prospective clinical trials subsequently.