〔Abstract〕 ObjectiveTo explore the correlation between the polymorphisms of the solute carrier family7 member11 ( SLC7A11)gene and the risk of non-cardia gastric cancer (NCGC) as well as the infection of Helicobacter pylori ( H.pylori). MethodsA total of 435 patients with NCGC and 479 healthy individuals undergoing physical examinations were included. The polymorphisms of the SLC7A11 gene (rs7674870, rs11734488, rs12506138, rs10022036) were genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. The influence of each locus on H. pylori infection and the occurrence of NCGC was analyzed. ResultsNo significant associations were found between SNP rs7674870, rs11734488, and rs12506138 and H. pylori infection ( P>0.05). The CT genotype and CC genotype of rs12506138, when in a codominant model, reduced the risk of developing NCGC compared to the TT genotype; the A-C-C and A-T-C haplotypes constructed by SLC7A11 rs7674870, rs11734488, rs12506138 were associated with a reduced risk of NCGC; the A-T-T and G-C-C haplotypes were associated with an increased risk of NCGC. Conclusion SLC7A11 rs7674870 and rs11734488 are not pivotal genetic loci for H. pylori infection and the pathogenesis of NCGC. SLC7A11 rs12506138 acts as a protective genetic locus for NCGC and antagonizes its oncogenic progression. The haplotype composed of the above three loci participates in regulating the overall genetic susceptibility to NCGC.