Oral cancer, representing 2-4% of all cancer cases, predominantly consists of Oral Squamous Cell Carcinoma (OSCC), which makes up 90% of oral malignancies. Early detection of OSCC is crucial, and identifying specific proteins in saliva as biomarkers could greatly improve early diagnosis. Here, we proposed a strategy to pinpoint candidate biomarkers. Starting from a list of salivary proteins detected in 10 OSCC patients and 20 healthy controls, we combined a univariate approach and a multivariate approach to select candidates. To reduce the number of proteins selected, a Protein-Protein Interaction network was built to consider only connected proteins. Then, an over-representation analysis (ORA) determined the enriched pathways. The network from 172 differentially abundant proteins highlighted 50 physically connected proteins, selecting relevant candidates for targeted experimental validations. Notably, proteins like Heat shock 70 kDa protein 1A/1B, Pyruvate kinase PKM, and Phosphoglycerate kinase 1 were suggested to be differentially regulated in OSCC patients, with implications for oral carcinogenesis and tumor growth. Additionally, the ORA revealed enrichment in immune system, complement, and coagulation pathways, all known to play roles in tumorigenesis and cancer progression. The employed method has successfully identified potential biomarkers for early diagnosis of OSCC using an accessible body fluid.