The present investigation was designed to evaluate salivary IL-8 and IL-6 levels in premalignant and OSCC patients, in order to verify the effectiveness of using them as diagnostic biomarkers for detection of OSCC and possibly early malignant transformation in premalignant lesions. This study utilized ELISA technique in order to assess the levels of IL-8 and IL-6 in whole unstimulated saliva. The ELISA system is cited as the most sensitive, well-established, and widely available protein-based testing platform for the detection of specific proteins in body fluids or tissue. The present study was carried out on 50 subjects where they were subdivided into 15 patients suffering from frank oral malignancy, 20 patients with oral premalignant lesions. Among the 20 patients, biopsy results enabled us to further subdivide the group into patients with dysplastic lesions and others with no dysplastic changes; 10 patients into each group. And 15 systemically healthy control. The control group was selected to match the premalignant and malignant groups regarding age and gender, with no oral mucosal lesions. The results showed that salivary IL-6 and IL-8 levels were higher in all the studied groups. Also the control group had the lowest level of IL-6 and IL-8 in the saliva. As for the OSCC group they showed the highest levels of IL-6 and IL-8 in the saliva when compared to both the OPL and the control groups, thus it could be concluded that salivary IL-6 and IL-8 might be a potential biomarker for the detection of OSCC. So, salivary IL-6 and IL-8 hold promise as biomarkers for OSCC. And also, analysis of cytokines as IL-6 and IL-8 in saliva may be one of predictive means to reflect the trend of malignant transformation of oral premalignant lesions