Background: Metformin has been shown to decrease cancer incidence, recurrence and improve overall survival among DM patients with various malignancies. Evidence indicates that metformin may suppresse growth and viability of HNSCC via different mechanism of action. In this study we investigate the potential clinical benefit of metformin in HNSCC patients. Methods: Retrospective analysis of patients with diagnosis of squamous cell carcinoma arising from oral cavity, oropharynx, hypopharynx and larynx from 2004 to 2012 at our institution was performed. DM patients and Metformin users were identified. Clinical data such as Age, Sex, smoking, TNM stage and overall survival (OS) were analyzed for all patients. Statistical analysis was performed with S-PLUS Version 7.0. Results: A total of 743 patients with HNSCC origin were identified. Among those patients, there were 485 patients with non-laryngeal carcinoma and 258 patients with laryngeal carcinoma. 166 (22.3%) of the cohort had DM. Of those DM patients, 63 (37.9%) were on metformin therapy. There were no significant clinical differences between Diabetic patients including patients who were on metformin and non-diabetic patients in terms of sex, age, TNM stage at diagnosis, and smoking history. The median OS for all patients with SCC of head and neck origin who are diabetic was 3.3 years versus 5.3 years for non diabetic patients (p<0.005). Median overall survival for diabetic patients with laryngeal SCC was 3.5 years versus 4.9 years for non diabetic patients (p=0.128). Median OS for diabetic patients with non-laryngeal SCC was 2.5 years versus 5.7 years for non diabetic patients (p<0.019). Laryngeal SCC patients on metformin had a median OS of 3.53 years versus 3.39 years for non-users (p=0.942). For non-laryngeal SCC patients on metformin median OS was 3.1 years versus 2.5 years for non-users (p=0.691). Conclusions: Patients with HNSCC and DM had worse median OS as compared to patients without DM. Metformin use showed a 6 month improvement in survival in non-laryngeal HNSCC which was not statistically significant due to sample size. Clinical studies specifically designed to evaluate the efficacy of metformin as an anticancer agent in oral and oropharyngeal SCC are warranted.