Helicobacter pylori infection elevates the risk of gastric diseases, including peptic ulcer and gastric cancer. Persistent infection is the first step to induce H. pylori-induced multistage diseases. Although the roles of genetic traits on persistent infection have not yet been elucidated, some individuals escape from persistent infection. Possible favorable conditions for H. pylori seem to be low acid secretion, reduced innate immune responses, and easier binding to gastric epithelial cells. IL-1β and TNF-α inhibit acid secretion. The genetic polymorphisms associated with both molecules have the potential to be the genetic traits underlying persistent infection. Functional polymorphisms associated with innate immune responses could also be involved with the genetic traits, but no polymorphisms with consistent associations have been identified so far. The polymorphisms associated with molecules for adhesion to epithelial cells are candidates of genetic traits, but more research is needed.