Background and Purpose: Head and neck malignancies remain a major global health burden, with poor survival outcomes despite advances in treatment. This study aims to identify key factors influencing progression-free survival (PFS) and overall survival (OS) in head and neck cancer patients, and to assess the impact of tumor characteristics, surgical margins, and postoperative therapies. Materials and Methods: A retrospective analysis was conducted on 306 patients with head and neck tumors treated between 2017 and 2022. Demographic data, tumor classification, surgical margins, and postoperative treatments were collected. Survival data were analyzed using univariate and multivariate methods to identify factors influencing PFS and OS. Results: Key determinants of survival identified include T and N categories,initial frozen section margins, postoperative recurrence, and adjuvant chemotherapy and radiotherapy. Patients with advanced T and N stages or initial positive frozen section margins exhibited significantly lower PFS and OS. Multivariate analysis further established postoperative chemotherapy as an independent factor negatively associated with PFS, potentially reflecting its application in advanced cases with poorer prognosis. Subgroup analysis revealed significant survival differences across tumor types, particularly between oral and salivary gland cancers. Conclusion: These findings underscore the need for individualized treatment strategies and more precise intraoperative assessments to improve outcomes. Future prospective studies are necessary to corroborate these findings and support evidence-based clinical decision-making.