Background: The aim of the current study was to assess and compare the expression of IL6, IL8, CD44 in patients with oral potential malignant diseases and oral squamous cell carcinoma. Methodology: A total of 100 subjects were selected and divided into three groups: - Oral premalignant diseases (OPMD) group consisted of 40 patients, Oral squamous cell carcinoma (OSCC) group consisted of 40 patients who were recently diagnosed with OSCC and Healthy group consisted of 20 healthy volunteers as controls with no oral or systemic lesions. Demographic variables such as age, gender, site of the lesion & habits were recorded for all patients. Unstimulated saliva samples were collected and analyzed for the expression of salivary biomarkers namely IL-6, IL-8 and CD44 using ELISA and the readings were calculated with the UV Spectrophotometer at 450nm. Results: The results of the present study showed that the higher percentages of males had OSCC and OSMF. Among the various sites of the oral cavity, buccal mucosa showed a higher prevalence of OSCC. Tobacco chewing habit was seen to be prevalent in OSMF and OSCC groups when compared with the other habits. IL-6, IL-8 and CD44 expression was found to be elevated in the OSCC group followed by OPMD however IL-6 levels was found to be statistically significant (p value=0.005). Conclusion: From the results of the present study, we inferred that IL-6 can be used as a potential salivary biomarker in the early identification and prevention of precancerous lesions and can be used as a therapeutic tool in assessing the risk for the progression of oral squamous cell carcinoma.