We carried out a hospital-based case-control study to investigate the role of XRCC1 gene Arg399Gln, Arg280His, and Arg194Trp polymorphisms in susceptibility to gastric cancer. A total of 214 gastric cancer patients and 247 control subjects were recruited between March 2013 and March 2015, and polymorphism genotype frequencies were determined by polymerase chain reaction-restriction fragment length polymorphism. Using the chi-square test, we detected statistically significant differences in age (chi-square = 22.25, P < 0.001), gender (chi-square = 6.74, P = 0.01), and family history of cancer (chi-square = 4.73, P = 0.03) between the case and control groups. Logistic regression analysis revealed that the XRCC1 Arg194Trp TT genotype conferred increased susceptibility to gastric cancer compared to the CC genotype [odds ratio (OR) = 2.38, 95% confidence interval (CI) = 1.28-4.49]. Moreover, individuals carrying the T allele of this variant were found to be at moderately increased risk of this disease (OR = 1.56, 95%CI = 1.16-2.09). However, the XRCC1 Arg399Gln and Arg280His polymorphisms were shown to have no influence on the development of gastric cancer. In conclusion, we suggest that the XRCC1 gene Arg194Trp polymorphism is associated with gastric cancer susceptibility in the Chinese population.