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To examine the association between anIL6(Interleukin-6) polymorphism (C-634G or rs1800796) and tooth loss, and an interaction between the polymorphism and smoking habits for the loss.Our subjects were 4917 check-up examinees ages 35–69. They reported tooth loss and lifestyle in a questionnaire. We regressed the number of teeth on theIL6genotype, gender, age, smoking, drinking, diabetes, hypertension, physical activity, energy intake, education, and brushing. We further estimated multivariate-adjusted odds ratios (ORs) for having <20 teeth.Participants with a GG genotype tended to have less teeth than those with CC;β= −0.798 (95% confidence interval [CI] = −1.501–−0.096). Subjects with a GG genotype were more likely to have <20 teeth than those with CC; OR was 1.56 (95% CI = 1.08–2.25). Association between current smoking and tooth loss was stronger among those with GG than among those with CC. In a multiple regression analysis, a significant interaction was found between GG genotype and current smoking in the prediction of tooth loss (P=0.018).TheIL6C-634G polymorphism was significantly associated with tooth loss. Our results suggest greater effects of smoking on tooth loss in GG genotype individuals.