〔Abstract〕 Objective To investigate the role of single nucleotide polymorphisms(SNP) of glutathione peroxidase 4(GPX4) gene in the risk of non-cardia gastric cancer. Methods A total of 1 031 samples were selected, including 506 normal examiners and 525 patients with non-cardia gastric cancer.GPX4rs4807542, rs713041, rs2074451 and rs3746162 were genotyped by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP). Unconditional Logistic regression was used to analyze the relationship between each SNP with the risk of non-cardia gastric cancer under the four genetic models. Results The CT+TT genotype of rs713041 reduced the risk of non-cardia gastric cancer compared with the CC genotype(OR=0.699, 95%CI: 0.537-0.910). The GT+TT genotype of rs2074451 reduced the risk of non-cardia gastric cancer compared with the GG genotype(OR=0.681,95%CI: 0.520-0.893). The G-C-G-C haplotype, constructed by the four SNPs ofGPX4, was related to an increased risk of non-cardia gastric cancer(OR=1.262, 95%CI: 1.035-1.539), and G-T-T-C haplotype was related to a decreased risk of non-cardia gastric cancer(OR=0.784, 95%CI: 0.656-0.937). The fourth-order interaction ofGPX4rs4807542, rs713041, rs2074451 and rs3746162 played a synergistic effect in the risk of non-cardia gastric cancer(P<0.05). Conclusion GPX4rs713041 and rs2074451 are related to non-cardia gastric cancer susceptibility. The G-C-G-C haplotype composed ofGPX4rs4807542, rs713041, rs2074451 and rs3746162 is a risk factor for non-cardia gastric cancer, while the G-T-T-C haplotype is a protective factor. The interaction betweenGPX4rs4807542, rs713041, rs2074451 and rs3746162 is closely connected with the occurrence of non-cardia gastric cancer.