Abstract:Helicobacter pylori (H. pylori) is a strong risk factor for gastric disease ranging from chronic gastritis to gastric cancer. But the mechanisms underlying the pathogenesis of H. pylori are still not completely understood.The cytotoxin-associated gene A (CagA) of H. pylori, an important virulence factor and the only bacterial oncoprotein, is extensively studied. CagA is delivered into gastric epithelial cells via type IV secretion of H. pylori. Upon delivery, CagA perturbs multiple host signaling pathways by interacting with the host signaling molecules, resulting in cytopathic effects and subsequent cell transformation. Some animal experiments also provide in vivo evidence for the oncogenic capacity of CagA. In this review, recent advances in the structural property, delivery manner and pathogenesis of CagA are summarized, which we hope could better explain the CagA-mediated pathogenesis of Helicobacter pylori and provide directions for the future approach.