Abstract: Objective To evaluate the safety, feasibility of long-term temozolomide chemotherapy (TMZ＞ 6 cycles) on high grade glioma patients. Methods Ninety-three high-grade glioma patients in Chinese PLA General Hospital from 2008 to 2015 were divided into TMZ＞ 6 cycles group and TMZ 6 cycles group. There were no significant differences in age, gender, pathologica grade, surgical method between two groups (P＞ 0.05). The differences between two groups in progression free survival (PFS) and overall survival (OS) were evaluated, and the survival curves of two groups were depicted by Kaplan-Meier method. Results Both OS and PFS of patients in TMZ＞ 6 cycles group were significantly longer than those of patients in TMZ 6 cycles group (PFS: 29 months vs 21 months, P=0.035; OS: 39 months vs 28 months, P=0.011), and the most common seen adverse reactions of grade 3 o above in patients after taking TMZ were thrombocytopenias (6.45%) and leucopenia (9.68%), which all occurred within 6 cycles. No obvious adverse reaction was observed in prolonged TMZ cycles. Conclusion Long-term treatment with temozolomide (TMZ＞ 6 cycles) is efficacious in prolonging PFS and OS for high grade glioma patients without additional side-effects.