A highly selective, label-free, surface-enhanced Raman spectroscopy (SERS) based sensor platform employing hollow carbon nanofibers functionalized with silver nanoparticles (Ag@HCNFs) has been developed to monitor anomalous concentrations of potential biomarkers, such as salivary nitrite facilitating pre-diagnosis of oral cancer. Co-axial electrospinning was used for the fabrication of the nanofibrous Ag@HCNFs followed by thermal treatment of PAN/PVP core-shell nanofibers and chemical reduction of silver nanoislands. The developed plasmonic Ag@HCNFs was structurally and morphologically characterized using X-Ray diffraction, Raman spectroscopy, scanning electron microscopy, and transmission electron microscopy, which clearly demonstrated the successful anchoring of silver nanoparticles on hollow carbon nanofibers. The properties of Ag@HCNFs showed significant SERS enhancement of the order of 107 with a detection limit of 10-11 M with R6G, demonstrating its efficacy to investigate real-time salivary samples, particularly towards the detection of salivary nitrite within the clinically relevant range (50 μM-300 μM) towards the pre-diagnosis of oral cancer. The proposed SERS-based salivary platform has the potential to be used as a low-cost, non-invasive pre-diagnostic tool for early diagnosis and mass screening of oral cancer.