Helicobacter pylori (H. pylori) infection induces apoptosis in gastric epithelial cells, and this occurrencemay link to gastric carcinogenesis. However, the regulatory mechanism of H. pylori-induced apoptosis is notclear. MicroRNA-146a has been implicated as a key regulator of the immune system. This report describes ourdiscovery of molecular mechanisms of microRNA-146a regulation of apoptosis in human gastric cancer cells.We found that overexpression of microRNA-146a by transfecting microRNA-146a mimics could significantlyenhance apoptosis, and this up-regulation was triggered by COX-2 inhibition. Furthermore, we found thatmicroRNA-146a density was positively correlated with apoptosis rates in H. pylori-positive gastric cancertissues and intratumoral microRNA-146a density was negatively correlated with lymph node metastasis amongH. pylori-positive gastric cancer patients. Understanding the important roles of microRNA-146a in regulatingcell apoptosis in H. pylori infected human gastric cancer cells will contribute to the development of microRNAtargeted therapy in the future.