Objectives: The present study was designed to evaluate serum and salivary IL-8 in premalignant and oral squamous cell carcinoma (OSCC) patients, in order to verify the effectiveness of salivary IL-8 as a diagnostic tool in detecting OSCC lesions. Materials and methods: 55 individuals were subdivided into 3 groups, 20 patients suffering from oral squamous cell carcinoma lesions, 20 patients suffering from oral premalignant lesions (OPL) and 15 individuals having age, gender and periodontal status matched with both patients groups acting as a control group. Serum and whole unstimulated saliva samples were collected from all the included groups in order to determine IL-8 level in both saliva and serum utilizing the ELISA technique. Results: The results showed that salivary IL-8 levels were higher than the serum levels in all the studied groups. Also the control group had the lowest level of IL-8 in both saliva and serum. As for the OSCC group they showed the highest levels of IL-8 in both saliva and serum when compared to both the OPL and the control groups. Conclusion: salivary IL-8 might be a potential biomarker for the detection of OSCC. Moreover, salivary IL-8 might be a useful detector of malignant transformation in OPL.