Abstract: Objective To investigate the association between selenoprotein S(SelS) gene G-105A,G-254A polymorphisms and genetic susceptibility to gastric cancer in Hu'nan Han population. Methods Polymerase chain reaction restriction fragment length of polymorphism (PCR-RFLP) was taken to detect the genotypes and allele frequencies of the SelS in 113 gastric cancer patients in Hu'nan Han population and 111 agematched healthy controls, to analyze the differences of allele and genotype frequencies of G-105A and G-254A. Results Genotype frequencies of GG, GA, AA in SelS G-105A loci were 100.0%, 0.0%, 0.0% in gastric cancer group, and 100.0%, 0.0%, 0.0% in control group respectively. Allele frequencies of G, A were 100.0%, 0.0% in gastric cancer group and 100.0%, 0.0% in control group respectively. There was no difference of genotype and allele frequencies of SelS G-105A polymorphism between gastric cancer group and control group. Genotype frequencies of CC, CT, TT in SelS G-254A were 50.0%, 37.2%, 12.8% in gastric cancer group and 65.8%, 28.8%, 5.4% in control group respectively. Allele frequencies of C, T were 69.0%, 31.0 in gastric cancer group and 80.2%, 19.8% in control group respectively. There were significant differences of genotype and allele frequencies of SelS G-254A polymorphism between gastric cancer group and control group (P<0.05). The relative risk of suffering from gastric cancer in Hu'nan Han population with T allele was 1.89 times of those with CC genotype (OR=1. 89, 95%CI:1.10-3.23). Conclusion SelS G-254A polymorphism is associated with the risk of gastric cancer. T allele may be a risk factor for gastric cancer in Hu'nan Han population. There may be no G-105A polymorphism distribution in Hu'nan Han population.