Autophagy is an intracellular catabolic process that is required to maintain cellular homeostasis. Pathogen-elicited host cell autophagy may favour containment of infection or may help in bacterial survival. Pathogens have developed the ability to modulate host autophagy. The secreted antigen HP0175, a peptidyl prolylcis,transisomerase ofHelicobacter pylori, has moonlighting functions with reference to host cells. Here we show that it executes autophagy in gastric epithelial cells. Autophagy is dependent on the unfolded protein response (UPR) that activates the expression ofPKR-likeERkinase (PERK). This is accompanied by phosphorylation of eukaryotic initiation factor 2α (eIF-2α) and transcriptional activation ofATF4andCHOP. Knockdown of UPR-related genes inhibits the conversion of LC3I to LC3II, a marker of autophagy. The autophagy-inducing ability ofH. pyloriis compromised when cells are infected with an isogenichp0175mutant. Autophagy precedes apoptosis. Silencing ofBECLIN1augments cleavage of caspase 3 as well as apoptosis. Increased apoptosis of gastric epithelial cells is known to be linked toH. pylori-mediated gastric inflammation and carcinogenesis. To the best of our knowledge, this study provides the first demonstration of how HP0175 endowed with moonlighting functions links UPR-dependent autophagy and apoptosis duringH. pyloriinfection.