The association between cheilitis granulomatosa and dental infections (dental caries and apical periodontitis) is still not well understood. Herein, we aimed to investigate the association in large hospital cases with cohort controls. Cheilitis granulomatosa cases (n = 181) were retrieved from Peking University Hospital of Stomatology and age- and sex-matched to controls (n = 181). The chi(2)-test, Student's t-test, and Mann-Whitney U-test were used to compare the differences between groups. The chi(2)-test and odds ratio were used to verify if there was an association and risk relationship. The results showed that both dental caries and apical periodontitis were associated with cheilitis granulomatosa (p < 0.001). Individuals with cheilitis granulomatosa had approximately a twofold increased frequency of dental caries than those without cheilitis granulomatosa (104/181, 57.5% vs. 53/181, 29.3%) (p < 0.001). The odds ratio of dental caries occurring in the case group compared to the control group was 3.211. The frequency of apical periodontitis in patients with cheilitis granulomatosa was significantly greater than in those without cheilitis granulomatosa (109/181, 60.2% vs. 28/181, 15.5%) (p < 0.001). The odds ratio was 8.272. Moreover, apical periodontitis was also locationally related to cheilitis granulomatosa (p < 0.001). Collectively, our study showed that the foci of dental infections are associated with cheilitis granulomatosa, suggesting that proper treatment of focal teeth may be important in the management of cheilitis granulomatosa.