significant for the precaution of gastric cancer risk population. Aims:To explore gastric cancer susceptibility gene profiling in an area in Shanghai,and to assess the risk of gastric cancer susceptibility. Methods:A total of 152 patients with primary gastric cancer at Shanghai Pudong Hospital were enrolled,and 152 demographic characteristics matched patients with non-gastrointestinal diseases,non-tumor were served as controls. Gene polymorphism was determined by allele specific polymerase chain reaction. Susceptibility gene of gastric cancer was screened. Multiple genes interactions were analyzed and multiple genes risk was evaluated by DEMCHUK model. Results:Univariate analysis showed that CYP2E1,NAT2M1,NAT2M2,NAT2,XRCC1194,MTHFRA1298C,VDR TaqⅠ were susceptibility genes of gastric cancer. Multivariate analysis showed that CYP2E1(C1/ C1),NAT2M1(T/ T),NAT2M2(A/ A),XRCC1194( T/ T)and MTHFRA1298C(A/ C)were susceptibility genotypes. Synergistic effect was found between genes except MTHFRA1298C (A/ C)with NAT2M1(T/ T)and NAT2M2(A/ A)(P ﹤0. 05). Multiple genes risk analysis showed that combination OR of multiple genes was highly correlated with gene frequency,and the risk of gastric cancer was increased with the increasing number of susceptibility genes. Conclusions:CYP2E1(C1/ C1),NAT2M1(T/ T),NAT2M2( A/ A),XRCC1194( T/ T) and MTHFRA1298C( A/ C) are susceptibility genotypes of gastric cancer. Carrying multiple susceptibility genes can significantly increase the risk of gastric cancer.