The objective was to analyze the relation between gastric cancer susceptibility and gene polymorphism, providing a reference for epidemiologic research of gastric cancer etiology. Two hundred and eighty gastric cancer cases were selected, and 280 healthy cases with the same gender, age (± 5), and residence place were selected as control group, with proportion of 1:1. Tag single nucleotide polymorphism was used for screening polymorphism of caspase3, which was combined with logistic regression model and multi-point joint analysis to analyze relation between different genotypes and gastric susceptibility. In analysis of gene polymorphism of caspase3 intrinsic apoptotic pathway and gastric cancer susceptibility, polymorphism of CASP3 rs4647693, CASP3 rs12108497 and CASP3 rs4647610 increased gastric cancer risk (rs4647693: ORGA 1.61, 95 % CI 1.06-2.28; rs12108497: ORTC 1.55, 95 % CI 1.09-2.18; ORCC 2.45, 95 % CI 1.08-4.16; rs4647610: ORAG 1.71, 95 % CI 1.14-2.31; ORGG 1.60, 95 % CI 1.23-2.34). Gastric cancer risk of haplotype AGGC carrier was significantly higher than that of haplotype GGAT as control (OR 1.44, 95 % CI 1.07-2.19). Gene polymorphism and haplotype of caspase3 can increase gastric cancer risk. However, it still needs to be verified by a large-sample and multicenter epidemiologic research.