Abstract: Objective To observe the efficacy and safety of temozolomide(TMZ) combined with radiotherapy on patients with high-grade glioma(HGG), and to explore the prognostic factors for HGG patients. Methods We retrospectively analyzed the clinical data of 50 patients with newly diagnosed HGG treated with TMZ combined with radiotherapy. All patients were treated with three-dimensional conformal technique(3DCRT) or intensity-modulated radiotherapy(IMRT), and received oral TMZ75 mg/(m²·d) during radiotherapy; the adjuvant chemotherapy scheme TMZ(150-200) mg/(m²·d) for 5 days, 28 days as a cycle, was used after radiochemotherapy. We analyzed the clinical outcome and safety of those HGG patients. Multivariate analysis was used to analyze some factors related to prognostic significance, including gender, age, Karnovsky performance scores(KPS), excision degree, pathological grade, interval time between surgery and radiochemotherapy, radiotherapy techniques and adjuvant TMZ cycle number. Results With a median follow-up of 21.4 months (6.6-57.5 months), 28 patients had disease progression or recurrence, and 22 patients were dead. The 1-, 2-, 3-year overall survival(OS) and progression-free survival(PFS) rates were 85.8% and 71.8%, 54.9% and 44.2%, 51.2% and 44.2%, respectively. TMZ combined with radiotherapy was generally well tolerated and common side effects were nausea, vomiting, neutropenia and thrombocytopenia. Multivariate analysis showed that independently prognostic factors for OS were KPS, pathological grade and adjuvant TMZ cycles; those for PFS were excision degree, pathological grade and adjuvant TMZ cycle number. Conclusion TMZ combined with radiotherapy have good efficacy and safety on HGG patients. KPS, excision degree, pathological grade and adjuvant TMZ cycle number are the important prognostic factors for HGG patients.