We aimed to explore the role of IL-10 -592 A/C SNP in the susceptibility to gastric cancer through a systematic review and meta-analysis. Each initially included article was scored for quality appraisal. 17 studies were eligible for the meta-analysis. We adopted the most probably appropriate genetic model (recessive model). Potential sources of heterogeneity were sought out via subgroup and sensitivity analyses, and publication biases were estimated. IL-10-592 AA genotype is associated with the reduced risk of developing gastric cancer among Asians and even apparently observed among Asians high quality subgroup, suggesting IL-10-592 AA genotype may seem to be more protective from overall gastric cancer in Asian populations. IL-10-592 AA genotype is also associated with the overall reduced gastric cancer susceptibility in persons with H. pylori infection compared with controls without H. pylori infection, suggesting IL-10-592 AA genotype may seem to be more protective from overall gastric cancer susceptibility in persons infected with H. pylori. IL-10-592 AA genotype is not associated with either pathologic subtypes (intestinal or diffuse) or anatomic subtypes (non-cardia or cardia) of gastric cancer susceptibility. Genotyping methods like direct sequencing should be highly advocated to be conducted in future well-designed high quality studies among different ethnicities or populations.