Potentially functional polymorphisms can modulate protein activities and host's DNA repair capacity, thereby influencing cancer susceptibility. The association of the polymorphisms in the nucleotide excision repair core pathway genes and gastric cancer susceptibility remains largely unknown. Here, we systematically analyzed the associations between nine polymorphisms in four key genes (XPA, ERCC1, ERCC2, and ERCC4) in the nucleotide excision repair pathway and gastric cancer risk in a Chinese population including 1142 patients and 1173 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the risk associations. We observed that ERCC1 rs2298881 CA variant genotype was associated with an increased gastric cancer risk (CA vs. CC: adjusted OR [AOR]=1.33, 95% CI=1.09-1.62; dominant model: AOR=1.32, 95% CI=1.10-1.60). However, ERCC1 rs3212986 AA variant genotype was identified as a protective factor for gastric cancer (AA vs. CC: AOR=0.73, 95% CI=0.54-0.98; recessive model: AOR=0.72, 95% CI=0.54-0.96). Genotype-based mRNA expression analysis further indicated that the rs2298881 A allele was associated with decreased ERCC1 mRNA expression. In all, these results indicated that the ERCC1 polymorphisms may affect the risk of gastric cancer in the Chinese Han population.