Objective:To investigate the association between Klotho gene polymorphisms and the risk of gastric cancer in Jiangsu population. Methods:In a case-control study of 151 patients and 145 controls,we genotyped G-395A in the promoter region and C1818T in exon 4 of Klotho gene by PCR-restriction fragment length polymorphism(PCR-RFLP) methods. The association between the genetic polymorphisms and the risk of the cancer was further examined by multivariate analysis. Results:The frequency of the A allele of G-395A polymorphism in patients(39.7%) was significantly higher than that in controls(28.2%,P = 0.038), with the adjusted OR=1.66 and 95℅CI 1.02~2.72,which was more pronounced among subgroups of youger males,smokers and drinkers. However,the frequency of C1818T did not show any significant difference between the patients and control subjects(P = 0.80). The two polymorphisms were in linkage disequilibrium(D = 0.449,r = 0.187) and in compliance with Hardy-Weniberg equilibrium in control. None of the haplotypes were significantly associated with the presence of the gastric cancer. Conclusion:The G-395A polymorphism in Klotho gene may positively contribute to the etiology of gastric cancer in Jiangsu population.