Saliva as a diagnostic tool, is gaining attention world wide. Due to non-invasiveness of its collection and non-necessity of skilled technician for collection, and presence of sensitive biomarkers in saliva, it is considered as a worthwile diagnostic tool. Present study made an attempt to evaluate the status of proteins, sialic acid and oxidative stress in oral squamous cell carcinoma. Unstimulated whole saliva samples were collected from healthy controls and oral squamous cell carcinoma (OSCC) patients. Salivary levels of total proteins, free sialic acid, protein-bound sialic acid, malondialdehyde and glutathione were assayed by spectro-photometric methods. OSCC patients had higher salivary levels of total proteins, free sialic acid, protein-bound sialic acid and malondialdehyde, and lower levels of glutathione, when compared to healthy controls. The changes correlated with progression of cancer as evident by more pronounced changes of above biochemical parameters in well-differentiated cases of OSCC, compared to moderately differentiated OSCC and patients with pre-malignant le-sions of OSCC. Elevated levels of proteins and sialic acid suggest role of glycoproteins in carcinogenesis. Oxidative stress is involved in etiopathology of oral cancer, as evident from elevated malondialdehyde and decreased glutathione. Salivary parameters could be of use in diagno-sis and prognosis of oral cancer.