<p>The objective of this study was to investigate the histomorphological characteristics of <i>H. pylori</i> colonization in the gastric mucosa in relation to the strength of the host’s immune response. A total of 2,443 endoscopic biopsy specimens were collected from individuals infected with gastric <i>H. pylori</i>. A detailed histological examination and an immunohistochemical detection were conducted on these samples. Among these, 54 patients with high-grade intraepithelial neoplasia underwent endoscopic submucosal dissection; 21 with <i>H. pylori</i>-infected gastric cancer and 5 with fibromatosis-like undifferentiated carcinoma underwent surgical resection. <i>H. pylori</i> infection in the gastric mucosa progressed to the development of gastric cancer in the following six stages, also referred to as six phases: the mucous layer infection phase, the surface epithelial cell infection phase, the neck mucous cell compensatory phase, the lamina propria lesion phase, the proliferative zone stem cell phase, and the intraepithelial neoplasia phase. The histopathological characteristics of <i>H. pylori</i> infection-induced epithelial cell damage and immune cell involvement at different stages were identified in this study based on the degree and depth of gastric mucosal injury caused by <i>H. pylori</i> infection. Additionally, based on the host’s immune status, distinct histomorphological features and immunophenotypes corresponding to strong and weak immune responses were distinguished. Histomorphological analysis of gastric mucosa infected with <i>H. pylori</i> in combination with assessment of the body’s immune response can facilitate clinicians in implementing immune interventions tailored to different stages of the infection, thereby achieving precise and targeted treatment.</p>