This study investigates the impact of tobacco and alcohol use on the location of oral squamous cell carcinoma (OSCC). It analyzed data from 519 patients with primary OSCC diagnosed at Helsinki University Hospital between 2016 and 2020. The study found that the floor of the mouth (FOM) had a significantly higher odds ratio for a history of smoking and alcohol use compared to other sites (OR=25.78; 95% CI: 8.02–82.95; p<0.001). In contrast, gingival and buccal sites showed less association with smoking and alcohol use (OR=0.43 and 0.47, respectively). Older patients were less likely to have a history of smoking and alcohol use than younger patients. Tumor size (T3-4) and FOM were also associated with higher odds of smoking and alcohol use. The study concludes that FOM is almost exclusively related to conventional smoking and heavy alcohol use. The study also highlights that OSCC sites have different etiologies, with FOM being particularly sensitive to carcinogens due to its thin, non-keratinized mucosa and the pooling of carcinogens with saliva. The findings suggest that FOM is more susceptible to carcinogens than other sites, and that the role of carcinogens varies by site. The study also notes that the incidence of OSCC in non-smoking, non-drinking patients has increased, indicating that other factors may be involved. The study emphasizes the importance of considering site-specific differences in OSCC for treatment planning and prevention strategies.This study investigates the impact of tobacco and alcohol use on the location of oral squamous cell carcinoma (OSCC). It analyzed data from 519 patients with primary OSCC diagnosed at Helsinki University Hospital between 2016 and 2020. The study found that the floor of the mouth (FOM) had a significantly higher odds ratio for a history of smoking and alcohol use compared to other sites (OR=25.78; 95% CI: 8.02–82.95; p<0.001). In contrast, gingival and buccal sites showed less association with smoking and alcohol use (OR=0.43 and 0.47, respectively). Older patients were less likely to have a history of smoking and alcohol use than younger patients. Tumor size (T3-4) and FOM were also associated with higher odds of smoking and alcohol use. The study concludes that FOM is almost exclusively related to conventional smoking and heavy alcohol use. The study also highlights that OSCC sites have different etiologies, with FOM being particularly sensitive to carcinogens due to its thin, non-keratinized mucosa and the pooling of carcinogens with saliva. The findings suggest that FOM is more susceptible to carcinogens than other sites, and that the role of carcinogens varies by site. The study also notes that the incidence of OSCC in non-smoking, non-drinking patients has increased, indicating that other factors may be involved. The study emphasizes the importance of considering site-specific differences in OSCC for treatment planning and prevention strategies.