Updated project metadata. Tongue squamous cell carcinoma is characterised by poor prognosis and high metastatic events. Patients with unresectable tumors are benefiting from neoadjuvant chemotherapy (NACT) which surgical resection, and controls distant metastasis, and locoregional recurrence. However, resistance to NACT limit the success of the treatment regimen. In this study, we investigated the altered proteome and phosphoproteome of NACT resistant and sensitive cohort using Mass spectrometry-based proteomics. We carried out proteomic as well as phosphoproteomic analysis of treatment naïve tongue cancer patients whose response to NACT is recorded. Proteomic analysis revealed distinct protein expression between the responders and non-responders. The Phosphoproteomic analysis revealed kinases and the pathways associated with NACT resistance in tongue cancer.