Oral squamous cell carcinoma (OSCC) accounts for 95% among all head and neck cancers. Literature reveals saliva as a predictive, diagnostic and prognostic tool in carcinoma, inflammatory and genetic disorders. Expression of salivary interleukin-6 (IL-6) has been reported in patients with OSCC and in oral potentially malignant disorders (OPMDs). This study aims at the following objectives: • To evaluate the changes in the salivary levels of IL-6 in healthy individuals and those with chronic periodontitis (CP), OPMD and OSCC. • To compare the estimated levels of salivary IL-6 individually in healthy individuals and those with CP, OPMD and OSCC. • To assess the estimated levels of salivary IL-6 individually within histopathologically differentiated OSCC. • To analyse salivary IL-6 as a reliable biomarker in the diagnosis of OSCC. Totally, 60 patients were divided into four groups consisting of 15 patients in each group. Salivary samples were collected by simple drooling method. The concentration of IL-6 is to be determined by using Quantitative sandwich ELISA technique. All analyses were carried out using Statistical Package for Social Sciences (SPSS). The concentration values of IL-6 were found to be more in OSCC group in comparison with the other three groups and the concentration values of OPMD were found to be more than in the CP and control group and was statistically significant. We attempted a study to evaluate the salivary IL-6 in patients with OSCC, OPMDs and CP in comparison with the healthy controls. We achieved a pragmatic result showed that salivary IL-6 can be a reliable biomarker in the detection of OSCC. Saliva, due its wide array of functional characteristics, is an upcoming diagnostic fluid in the field of medicine and salivary IL-6 can be one such biomarker in the diagnosis of OSCC.