Most of the studies dealing with Chronic Mechanical Irritation (CMI) and Oral Cancer (OC) only considered prosthetic and dental variables separately, and CMI functional factors are not registered. Thus, the aim of this study was to assess OC risk in individuals with dental, prosthetic and functional CMI. Also, we examined CMI presence in relation to tumor size. A case-control study was carried out from 2009 to 2013. Study group were squamous cell carcinoma cases; control group was patients seeking dental treatment in the same institution. 153 patients were studied (Study group n=53, Control group n=100). CMI reproducibility displayed a correlation coefficient of 1 (p<0.0001). Bivariate analysis showed statistically significant associations for all variables (age, gender, tobacco and alcohol consumption and CMI). Multivariate analysis exhibited statistical significance for age, alcohol, and CMI, but not for gender or tobacco. Relationship of CMI with tumor size showed no statistically significant differences. CMI could be regarded as a risk factor for oral cancer. In individuals with other OC risk factors, proper treatment of the mechanical injuring factors (dental, prosthetic and functional) could be an important measure to reduce the risk of oral cancer.