Xeroderma pigmentosum group G (XPG), one of key components of nucleotide excision repair pathway (NER), is involved in excision repair of UV-induced DNA damage. Single nucleotide polymorphisms (SNPs) in the XPG gene have been reported to associate with the clinical outcome of various cancer patients. We aimed to assess the impact of four potentially functional SNPs (rs2094258 C>T, rs2296147 T>C, rs751402 G>A, and rs873601 G>A) in the XPG gene on prognosis in colorectal cancer (CRC) patients. A total of 1901 patients diagnosed with pathologically confirmed CRC were genotyped for four XPG polymorphisms. Cox proportional hazards model analysis controlled for several confounding factors was conducted to compute hazard ratios (HRs) and 95% confidence intervals (CIs). Of the four included SNPs, only rs2296147 was shown to significantly affect progression-free survival (PFS) in CRC. Patients carrying rs2296147 CT/TT genotype had a significantly shorter median 10 years PFS than those carrying CC genotype (88.5 months vs. 118.1 months), and an increased progression risk were observed with rs2296147 (HR=1.324, 95% CI=1.046-1.667). Moreover, none of the four SNPs were associated with overall survival. In conclusion, our study showed that XPG rs2296147 CT/TT variants conferred significant survival disadvantage in CRC patients in term of PFS. XPG rs2296147 polymorphism could be predictive of unfavorable prognosis of CRC patients.