ObjectiveRadiation osteonecrosis of the skull base after radiotherapy for nasopharyngeal carcinoma is one of the most serious complications, affecting patient survival and quality of life. To date, surgical resection is the main treatment for radiation osteonecrosis. The repair after the operation is very important. Inappropriate repair or lack of repair can easily cause local infection that can even spread to the brain, aggravating osteonecrosis. This study aimed to verify the feasibility and safety of the anterolateral thigh free fascia flap in repairing large skull base defects. MethodsFrom June 2021 to July 2022, a total of 12 patients with a history of radiotherapy for nasopharyngeal carcinoma received surgical treatment at the Department of Otolaryngology Head & Neck Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine. All patients were diagnosed with radiation osteonecrosis of the skull base with large skull base defects. During the endoscopic operation, a free anterolateral thigh fascia flap was used to repair the skull base and complete vascular anastomosis reconstruction. The preoperative and postoperative pain scores were retrospectively analyzed, and the dynamic changes in endoscopic surgery sites were observed. ResultsThe 12 patients had a median age of 58 y, with 8 (66.7%) males and 4 (33.3%) females. The median headache score for the patients was 5 (4–7) before surgery. The patient's headache was significantly relieved postoperatively, with 11 patients having a score of 0 and one patient having a score of 1. The stench was completely resolved after the operation. There were no serious complications during the perioperative period or 12 months after the operation. ConclusionThe application of anterolateral thigh free fascia flap in skull base reconstruction is a safe and reliable reconstruction technique suitable for endoscopic surgical repair of large-scale skull base necrosis.