Oral squamous cell carcinoma (OSCC) contributes vastly to oral cancer and Oral submucous fibrosis (OSMF) is an ongoing, silent events related to high risk of malignancy. The poor prognosis of oral lesions is majorly due to late-stage diagnosis. We aimed to evaluate the diagnostic biomarker ability of Interleukin-6 (IL-6) in conjunction with alterations of Cancer stem cell (CSC) markers: CD44 and CD133 in the oral precancerous and cancerous subjects. A total of 135 individuals were enrolled in the study, in which 60 cancer cases (OSCC), 60 precancer controls (OSMF) and 15 healthy controls were included. Analysis of serum inflammatory cytokines IL-6 was evaluated by ELISA. Expression studies of CD133 and CD44 were performed by immunohistochemistry.