Abstract Objective The aim of this study is to investigate the relationship between oral problems and Helicobacter pylori (Hp) infection, and to reveal which oral problems are significantly related with Hp infection. Methods Participants undergoing healthy medical examination were examined for 12 kinds of oral problems: dental calculus, oral mucosal disease, periodontal disease, decayed tooth, tooth defect, disuse tooth, residual crown and root, devital tooth, loose tooth, fistula, ill-fitting fixed denture and ectopic tooth. Hp infection was confirmed by 13C–urea breath test. Participant information including age, educational level, smoking habits, drinking habits, height, weight and body mass index (BMI) were collected using a standard questionnaire. Results Hp infection was 46.97% of the 54,036 cases. Age (P<0.01), gender (P<0.001) and BMI (P<0.01) were significantly associated with Hp infection. Smoking (P<0.001) and regular drinking (P<0.001) were showed to be associated with Hp infection. After adjustments for other associated factors, in all of the 12 oral problems, only dental calculus [n=35,559, OR (95% CI)=1.05 (1.01–1.09), P=0.012] and loose tooth [n=2411, OR (95% CI)=1.22 (1.03–1.22), P=0.007] were related with Hp infection. Conclusion In a cross-sectional analysis, the prevalence of Hp infection was strongly related with several social problems, including age, gender, BMI, smoking and regular drinking. In addition, oral problems, particularly dental calculus and loose tooth, were found to be associated with Hp infection, possibly due to the dental plaque. The study suggested that to prevent or eradicate Hp infection, we need to focus on oral hygiene and prevention of oral problems, especially dental calculus and loose tooth.