Oral Squamous Cell Carcinoma (OSCC) is one of the most prevalent cancers in the world with the maximum number of cases reported from India. Poor survival rate associated with OSCC can be attributed to the non-availability of a biomarker, as one of the major reasons, leading to late presentation. Identification of an early diagnostic biomarker, which can also be used as a screening tool, will be helpful in reducing the disease morbidity and mortality. In this report, we present Parallel Reaction Monitoring (PRM) based validation of 12 candidate proteins, identified initially by tandem mass tag (TMT) based relative quantification of salivary proteins on LC-MS, in the saliva of Oral Squamous Cell Carcinoma (OSCC) cases (N=50) and healthy controls (N=49), AZGP1, AHSG, KRT6C, S100A7, S100A9, KLK1, BPIFB2, IGLL5, CORO1A, LACRT, LCN2 and PSAP. Heavy isotope labelled reference peptides were used to produce calibration curve and absolute quantification of proteins and resulting data were analyzed statistically using R. Salivary AHSG (p=0.0041**) and KRT6C (p=0.002**) were significantly upregulated in OSCC cases while AZGP1 (p<0.0001***), KLK1 (p=0.006**) and BPIFB2 (p=0.0061**) were significantly downregulated. Multivariate logistic regression modelling resulted in a better risk prediction model consisting of AZGP1, AHSG and KRT6C with p value <0.0001***. Using this model ROC with an area under the curve of 82.2% was produced and sensitivity and specificity observed for this model was 78% and 73.5%, higher than any of the individual proteins. Positive and negative predictive values for the model were 76% and 75% respectively. We report a potential biomarker panel consisting of proteins AZGP1, AHSG and KRT6C for early diagnosis of OSCC.