Helicobacter pylori (H. pylori) has coevolved with its human host for more than 100 000 years. It can safely colonize around the epithelium of gastric glands via their specific microstructures and proteins. Unless patients receive eradication treatment, H. pylori infection is always lifelong. However, few studies have discussed the reasons. This review will focus on the adhesion of H. pylori from the oral cavity to gastric mucosa and summarize the possible binding and translocation characteristics. Adhesion is the first step for persistent colonization after the directional motility, and factors related to adhesion are necessary. Outer membrane proteins, such as the blood group antigen binding adhesin (BabA) and the sialic acid binding adhesin (SabA), play pivotal roles in binding to human mucins and cellular surfaces. And this may offer different perspectives on eradication.