〔Abstract〕 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 , inclu- ding 506 normal examiners and 525 patients with non-cardia gastric cancer. GPX4 rs4807542 , 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 re- duced 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 of GPX4 , 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 of GPX4 rs4807542 , rs713041 , rs2074451 and rs3746162 played a syner- gistic effect in the risk of non-cardia gastric cancer (P < 0. 05) . Conclusion GPX4 rs713041 and rs2074451 are related to non-cardia gastric cancer susceptibility . The G-C-G-C haplotype composed of GPX4 rs4807542 , 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 between GPX4 rs4807542 , rs713041 , rs2074451 and rs3746162 is closely con- nected with the occurrence of non-cardia gastric cancer.