There are no early detection biomarkers or prognostic markers for oral squamous cell carcinoma (OSCC) thus many are detected late, with unpredictable disease course. Using systems level analysis on shotgun proteomics with quantitative label-free ultra-definition mass spectrometry, our study aims to find novel proteins involved in both low and high grade OSCC tissue, and to further understand pathways involved in cancer development and progression, using proteomic analysis.