Genetic variations in miRNAs have been demonstrated to be capable of altering miRNA expression, consequently affecting many cancer-related biological processes. The MIR196A2 rs11614913 (T > C) polymorphism has been reported to be associated with various cancers development and progression. In our study, we aim to explore whether this polymorphism is relevant to the genetic susceptibility and prognosis of gastric cancer in a Chinese population. We analyzed the correlations of rs11614913 polymorphism with gastric cancer susceptibility in test and validation sets. The test set comprised 749 cases and 900 controls, while the validation set enrolled 940 cases and 1046 controls. Moreover, we evaluated the association between the polymorphism and gastric cancer prognosis in the validation set with follow-up information. The variant rs11614913 CC genotype was associated with a significantly reduced risk of gastric cancer in both sets (adjusted odds ratio [OR] = 0.78, 95% confidence interval [CI] = 0.62–0.99 for the test set and 0.64, 0.52–0.80 for the validation set) compared with the CT/TT genotypes. Furthermore, the CC genotype was associated with a significantly increased survival of gastric cancer compared with the CT/TT genotypes (adjusted hazard ratio [HR] = 0.72, 95% CI = 0.55–0.95), and the association was more prominent among patients with non-cardia gastric cancer than those with cardia gastric cancer (adjusted HR = 0.57, 95% CI = 0.40–0.83 for NCGC and 1.00, 0.65–1.53 for CGC). Our results suggested that the genetic variation of MIR196A2 may play a role in gastric cancer tumorigenesis. © 2013 Wiley Periodicals, Inc.