Abstract: Background and purpose: Programmed death-ligand 1 (PD-L1) is of great importance in the process of colorectal cancer cell escaping from immune system. Therefore, the association between PD-L1 genetic variation and clinical outcomes of postoperative colorectal cancer patients receiving capecitabine-based adjuvant chemotherapy was investigated in this study. Methods: Designed as a retrospective analysis, a total of 213 colorectal cancer patients from Department of General Surgery, Tumor Hospital of Henan Province and Department of Anus and Intestine Surgery, the Third Affiliated Hospital of Henan University of Traditional Chinese Medicine underwent surgical treatment and received capecitabine-based adjuvant chemotherapy in this study. Baseline characteristics and the clinical outcomes data of the patients included in this study were managed. Peripheral blood and the postoperative tissue specimens of the colorectal cancer patients were collected for the genotyping of the genetic variation and PD-L1 mRNA expression, respectively. The correlation between genetic variation and other baseline characteristics was analyzed by Chi- square test and nonparametric test. The mRNA expression levels of PD-L1 in different genotypes were analyzed by nonparametric test. The univariate analyses of genotypes and prognosis were carried out by Kaplan-Meier survival analysis, and multivariate analyses were adjusted by Cox regression analysis. Results: In terms of the clinical outcomes, all of the 213 colorectal cancer patients were available for efficacy evaluation. The median disease-free survival (DFS) of the 213 colorectal cancer patients was 4.6 years, and the median overall survival (OS) was 6.5 years. The single nucleotide polymorphisms included in this study were collected in the database with the minor allele frequency >10% in Chinese population (rs2297136, rs822336 and rs822337). Of the polymorphisms analyzed, only rs2297136 was of clinical significance. The following was the prevalence of rs2297136 in the intron region among the colorectal cancer patients: TT genotype 148 cases (69.48%), TC genotype 59 cases (27.70%) and CC genotype 6 cases (2.82%). The minor allele frequency was 0.17. The distributions of three genotypes were in accordance with Hardy-Weinberg Equilibrium (P=0.967). Patients with TC and CC genotypes were merged in the comparison of prognosis. The survival analysis of patients with different genotypes showed that the median DFS of patients with TT genotype or TC/CC genotype was 4.7 and 3.3 years, respectively (P=0.001). The median OS was 6.5 and 4.7 years for the two genotypes respectively, which was statistically significant as well (P<0.001). Adjusted in multivariate Cox regression analysis for OS, TC/CC genotype was an independent factor for DFS (OR=1.89, P=0.006). Additionally, of the 79 postoperative tissue specimens, the results showed that the mRNA expression levels of PD-L1 in cancer tissues of the patients with TC/CC genotype were significantly higher compared with patients with TT genotype (P<0.001). Conclusion: The clinical outcomes of colorectal cancer patients receiving capecitabine-based adjuvant chemotherapy may be influenced by PD-L1 rs2297136 through mediating the mRNA expression of PD-L1.