Treponema denticola is a spirochete associated with periodontitis, an infectious disease that destroys tooth attachments. It appears that these organisms reach oral epithelial cells, where they undergo their own unique molecular mechanism before displaying the acquired phenotypes associated with cancer, including inhibition of apoptosis, proliferation, and increased migration of epithelial cells. With this background the objective is to study the presence of Treponema denticola in oral squamous cell carcinoma. Total of 30 oral squamous cell carcinoma and oral mucosal non-cancerous tissue specimens were collected from patients and controls respectively. Ribonucleic acid (RNA) isolation was done from each aseptically deliquesced tissue specimen using Trizol method and converted into complementary deoxyribonucleic acid (cDNA) followed by specific gene amplification of Treponema denticola by polymerase chain reaction. Treponema denticola was detected in 8 oral squamous cell carcinoma tissue samples. No control tissue specimen was found to be positive for Treponema denticola. Current study findings suggest that Treponema denticola could play a role in the pathogenesis of oral squamous cell carcinoma. © 2021 Elsevier B.V., All rights reserved.