The aim of the study was to explore the relations between the genetic polymorphism and the susceptibility to the gastric cancer in Chinese Han population, and to analyze the multi-genes risk in the development of gastric carcinoma. A case-control study of 1:1 matching was performed on 564 individuals with primary gastric carcinoma in Nanjing, China. The genotypes of CYP2E1, GSTMl, GSTTl, NAT2, ALDH2, MTHFR, XRCCl, IL-1β, VDR, and TNF were detected by molecular biological techniques (PCR-RFLP and AS-PCR). Sole gene and gene-gene interactions were analyzed using Logistic regression model. The effect of multi-genes on gastric carcinoma was analyzed using multi-gene risk analysis model, which focused on the effect of multi-gene interaction on the development of gastric carcinoma. The genotypes involved in the susceptibility of gastric carcinoma were CYP2E1(c1/c1), NAT2M1(T/T), NAT2M2(A/A), XRCC1194(T/T), NAT2 phenotype (slow acetylator), MTHFR1298(A/C), and VDR TaqI(T/T), respectively. Multi-gene risk analysis model was introduced to analyze the effect of these genes on the gastric carcinoma. The results showed that there was a strong relation between odds ratio (OR) value of polygene combination and the gene frequency. With the increase of susceptibility gene frequency, the risk distribution curve of gastric carcinoma would shift to a more dangerous phase and exhibit a quantitative relation. Our results demonstrated that the OR of each gene can be utilized as an index to assess the effect of multiple susceptible genes on the occurrence of gastric carcinoma.