Objective To investigate the efficacy and safety of teniposide superselective intra-arterial chemotherapy combined with bevacizumab in the treatment of recurrent high-grade glioma. Methods According to the treatment method，79 patients with recurrent high-grade glioma were divided into experimental group with 37 patients （teniposide intra-arterial chemotherapy combined with bevacizumab） and control group with 42 patients （bevacizumab monotherapy）. The two groups were compared in terms of objective response rate，disease control rate，and the incidence rate of adverse reactions，and the impact of the gene promoter methylation status of O⁶-methylguanine-DNA methytransferase on disease control rate was analyzed. Results The objective response rate was 43.2% in the experimental group and 21.4% in the control group（P=0.038），and the disease control rate was 78.4% in the experimental group and 54.8% in the control group（P=0.027）. Compared with the control group，the experimental group had significantly higher incidence rates of the adverse reactions such as mild gastrointestinal reactions（P=0.044），headache（P=0.044），and leucopenia（P=0.026）. Compared with the control group，the experimental group had a significantly higher disease control rate in the population aged <60 years（P<0.05）. Conclusion Teniposide superselective intra-arterial chemotherapy combined with bevacizumab has better efficacy than bevacizumab monotherapy in the treatment of recurrent high-grade glioma and thus holds promise for further clinical application.