Objective To explore the relationship between forkhead box P3(Fox P3)gene polymorphism and susceptibility to gastric cancer in Chinese Han population.Methods From January 2014 to December 2016,a total of 312 patients with primary gastric cancer and 548 age and gender matched controls were recruited.Polymorphisms of Fox P3 at rs3761548 and rs2232365 loci were analyzed by polymerase chain reaction-restriction fragment length polymorphism techniques(PCR-RFLP).Odd ratio(OR)and 95% confidence interval(CI)were used to analyze the correlation between different genotype and susceptibility to gastric cancer,clinical pathological characteristics of patients with gastric cancer.Results The frequency of AA,AC,and CC genotype of rs3761548 in gastric cancer group and control group were 22.8%(71/312),44.2%(138/312),33.0%(103/312)and 14.8%(81/548),48.5%(266/548),36.7%(201/548),respectively.AA genotype could increase the risk of gastric cancer(OR=1.711,95% CI 1.150 to 2.545,P=0.008).The frequency of A and G allele of gastric cancer group and control group were 44.9%(280/624),55.1%(344/624)and 39.1%(428/1 096),60.9%(668/1 096), respectively.A allele could increase the risk of gastric cancer(OR=1.270,95% CI 1.041 to 1.550,P=0.018).The frequency of AA,AG,and GG genotype of rs2232365 in gastric cancer group and control group were 19.2%(60/312),46.5%(145/312),34.3%(107/312)and 14.1%(77/548),48.7%(267/548),37.2%(204/548),respectively.In recessive model(AA vs AG+GG),AA genotype could increase the risk of gastric cancer(OR=1.456,95% CI 1.005 to 2.110,P=0.046).A allele of rs3761548 was associated with the depth of invasion in gastric wall(χ2 =12.710,P=0.001)and Helicobacter pylori infection(χ2 = 5.613,P= 0.018).A genotype could increase the risk of lymphatic metastasis(χ2 =4.878,P=0.027).Conclusion Fox P3 gene polymorphism is associated with the susceptibility to gastric cancer in Chinese Han population,and can be molecular-maker of poor prognosis of gastric cancer.