In this study, we found that PUMA is induced by H. pylori by Toll-like receptor 2 (TLR2)/NF-κB-mediated transcriptional regulation and contributes to GEC apoptosis, gastritis, and the progression of gastric cancer, which is significantly attenuated by genetic ablation of PUMA or TLR2. Here, TLR2 is linked to gastric cancer.