© 2020 The Authors. Clinical and Experimental Dental Research published by John Wiley & Sons Ltd Objectives: Serum level of vitamin D has been used as a predictor for cancer development. We intend to measure the baseline vitamin D level in patients with oral squamous cell carcinoma (OSCC) and to compare same with non-cancer controls to determine any association. Materials and methods: Patients with OSCC presenting to our clinics were included in this study. Their baseline serum vitamin D levels were measured prior to cancer treatment after obtaining their consents. These patients were then matched with at least 2 cancer-free subjects to serve as controls and whose serum vitamin D levels were also measured. The serum vitamin D levels obtained for the two groups were then categorized into normal (>35 ng/ml), mild deficiency (25–35 ng/ml), moderate deficiency (12.5–25 ng/ml), and severe deficiency (<12.5 ng/ml). The data were analyzed statistically and the two groups compared. Results: A total of 51 patients with OSCC (Male 22 [43%] and female 29 [57%]) and 113 cancer-free controls (Male 36 [31.86%] and female 77 [68.14%]) were included in the study. The commonest site for OSCC was the tongue, accounting for 45% of the cancer cases. Mean age for cancer patients was 59.33 years ±12.54 and 49.24 years ±15.79 for the control. Among the OSCC patients, 74.51% had moderate to severe vitamin D deficiencies, whereas only 20.35% had a moderate deficiency in the control group with no severe deficiency. Conclusion: Logistic regression analysis shows a positive association between vitamin D deficiency and OSCC risk especially in levels below 25 ng/ml. This further corroborates the assertion that vitamin D deficiency may be a useful indicator of OSCC. It may, therefore, be necessary to routinely prescribe vitamin D supplements to subjects with moderate to severe deficiencies in order to decrease the chances of OSCC development.