Radiation necrosis (RN) is one of the complications of radiotherapy. Angiogenesis is a key factor underlying the development of RN, and Endostar, a safe and well-tolerated recombinant human endostatin, has been used to treat a variety of tumors. Thus far, however, no definitive reports on the use of Endostar for RN treatment have been reported. Here, we report the successful treatment of one patient with symptomatic brain radiation necrosis (BRN) using Endostar in combination with short-term hyperbaric oxygen therapy (HBO). One triple-negative breast cancer patient with recurrent brain metastatic lesions after standard chemoradiotherapy was referred to a specialty center outside our hospital for stereotaxic radiotherapy. Two months later, the patient showed deteriorating clinical symptoms, and magnetic resonance imaging (MRI) showed radiation necrosis with significant surrounding edema. The patient had a poor response to mannitol and steroids. After diagnosing this patient with BRN, we began short-term HBO therapy and intravenously administered Endostar for 4 cycles. The patient responded well to this strategy, showing rapidly and dramatically improved MRI findings and clinical symptoms. No tumor progression was observed at 10 months after treatment. Endostar in combination with short-term HBO therapy had marked effects on symptomatic BRN. However, additional large-scale, double-blinded, controlled trials are necessary to confirm the clinical effect of Endostar in combination with a short-term HBO therapy regimen on BRN.