Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer and is major cause of cancer mortality and morbidity. It emerges within oral cavity, lip, tongue, floor of the mouth, nasopharynx, palate, gingival and larynx, is common cancer worldwide especially in Southeast Asia and Southern China. Despite of the advancements in the understanding of the HNSCC as the disease, the 5 year survival rate remains unchanged at 50% since last three decades. Factors such as advanced stage presentation of the patient and consequent delay in diagnosis contributes to the bleak scenario. Thus, therefore there is dire need of useful biomarkers that can predict HNSCC in early stages and can serve as prognostic indicators or targets for treatment. In the present study, We used iTRAQ (isobaric tags for relative and absolute quantitation)-based quantitative proteomic approach followed by liquid chromatography and high resolution tandem mass spectrometry (LC-MS/MS) to identify differential proteins from head and neck cancer cell lines.