One of the most prevalent malignant tumors of the digestive tract is gastric cancer (GC). Age, high salt intake,Helicobacter pylori(H. pylori) infection, and a diet deficient in fruits and vegetables are risk factors for the illness. A significant risk factor for gastric cancer is infection withH. pylori. Infecting gastric epithelial cells with virulence agents secreted byH. pylorican cause methylation of tumor genes or carcinogenic signaling pathways to be activated. Regulate downstream genes’ aberrant expression, albeit the precise mechanism by which this happens is unclear. Oncogene, oncosuppressor, and other gene modifications, as well as a number of different gene change types, are all directly associated to the carcinogenesis of gastric cancer. In this review, we describe comprehensiveH. pyloriand its virulence factors, as well as the activation of the NF-κB, MAPK, JAK/STAT signaling pathways, and DNA methylation following infection with host cells via virulence factors, resulting in abnormal gene expression. As a result, host-related proteins are regulated, and gastric cancer progression is influenced. This review provides insight into theH. pyloriinfection, summarizes a series of relevant papers, discusses the complex signaling pathways underlying molecular mechanisms, and proposes new approach to immunotherapy of this important disease.