ABSTRACT. We conducted a hospital-based case-control study to evaluate the association between polymorphisms in excision repair cross-complementing group 1-xeroderma pigmentosum group F (ERCC1-XPF) variants and the risk of colorectal cancer in a Chinese population. Genotyping of the ERCC1 rs2298881 and rs11615 and XPF rs2276466 polymorphisms were detected by polymerase chain reactionrestriction fragment length polymorphism. Colorectal cancer cases were more likely to be smokers, consume alcohol, have higher energy intake, and have a family history of cancer. Using conditional regression analysis, subjects carrying the ERCC1 rs2298881CC genotype and C allele showed a significantly increased risk of colorectal cancer compared with those carrying the AA genotype. However, we found no association between the rs11615 and rs2276466 polymorphisms and the risk of colorectal cancer. In conclusion, the ERCC1 rs2298881 polymorphism may be used as a predictive factor for determining the risk of colorectal cancer in a Chinese population. This finding may be ERCC1 and XPF and colorectal cancer useful for identifying the genetic characteristics of colorectal cancer and developing more efficient strategies for prevention and treatment.