Objectives: This study aimed to assess the hypothesis that recurrent denture-related sores association may be associated with the risk of oral cancer. Methods: We conducted a hospital-based case-control study comprising 71 new cases of oral cancer in two hospitals in São Paulo, Brazil, and 240 controls without cancer, recruited from outpatient units of the same hospitals. All cases had histologically confirmed squamous cell carcinoma in anatomic sites of the mouth that may be specifically consi-dered at risk of sores by ill-fitting dentures. Denture-related sores were assessed by the self-report of recurrent oral sores due to the use of ill-fitting complete removable dental prosthesis. Associations were assessed by multivariate logistic regression conditioned on socio-demographic and behavioral characteristics. Results: The association between ill-fitting dentures and oral cancer was statistically significant in the multivariate model: odds ratio 3.98; 95% confidence interval 1.06 - 14.96. The specific assessment of association between tumors in the lower jaw and sores by mandibular dentures confirmed this result: odds ratio 6.39; 95% confidence interval 1.49 - 29.52. Conclusion: The potential contribution of denture-related sores to oral carcinogenesis still fuels controversies. This study reinfor-ces the hypothesis that recurrent denture-related sores may be associated with the risk of oral cancer. Results reported here also suggest that an appropriate application and monitoring of dental prosthesis represent a non-negligible scope for cancer prevention.