Skull base osteoradionecrosis (ORN) is a serious late complication of radiotherapy in patients with nasopharyngeal carcinoma (NPC) that significantly affects their quality of life (QOL) and may be life-threatening. We aimed to report the clinical efficacy of endoscopic radical resection of the necrotic tissue and simultaneous skull base repair for patients with ORN.We enrolled 39 patients with ORN who underwent endoscopic radical necrotic tissue resection with concomitant skull base repair using muscle or mucosal flaps at our institution. The 5-year overall survival (OS) was determined. Pain, foul odor, epistaxis, and QOL at different time points were assessed using a visual analog rating scale (VAS), and factors affecting OS and QOL were analyzed. The OS rates at 1, 3, and 5 years were 88.33 %, 71.46 %, and 53.60 %, respectively. Internal carotid artery (ICA) risk and serum hemoglobin levels significantly affect patient OS. From 1 week preoperatively to 6 months postoperatively, the patients' VAS scores for pain, foul odor, and epistaxis decreased significantly from 3.81, 2.70, and 1.81 to 0.73, 0.49, and 0.08, respectively (P < 0.001), whereas the QOL score increased from 6.09 to 7.86 (P < 0.001). ICA risk significantly affects patient QOL. Endoscopic necrotic tissue resection combined with skull base repair is safe and effective for treating patients with ORN, significantly relieving their symptoms and improving their QOL. Accurately assessing ICA rupture risk and nutritional status and rational intervention are important in patients with ORN.Copyright © 2025 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.