Objective To investigate the efficacy of treatment on malignant intracranial gliomas with the chemotherapy of intracerebral implantation of 5-Fu biodegradable polymers combined with radiotherapy of interstitial implantation of 125Ⅰ after microsurgery resection. Methods Sixty-five patients with malignant intracranial gliomas who had underwent craniotomy microsurgical resection were intraoperatively implanted in the tumor bed around with 5-Fu biodegradable polymers and 125Ⅰ seeds. After first implantation (3 months to 1 year), stereotactic guided implantation was carried out 1 or 2 times again. The patients were followed up for 6-36 months to observe the efficacy, edema and adverse reactions, compared with follow-up of 40 patients with malignant intracranial gliomas treated by conventional radiotherapy and chemotherapy after microsurgical total resection. Results Within 1 week after the implantation the patients had headache significantly, WBC of cerebrospinal fluid was increased to some degrees, and edema was obvious compared with surgery alone. All patients were treated and discharged. Forty-four patients were completely followed-up and the survival period was significantly longer. Within 6 months, 1 year, 2 years and 3 years, there were 4 cases (9.1 %) of recurrence and no case of death, 14 cases (31.8 %) of recurrence and no case of death, 20 cases (45.5 %) of recurrence and 12 cases (27.6 %) of death and 29 cases (65.9 %) of recurrence and 20 cases(45.5 %) of death, respectively. No obviously adverse reactions were found and the quality of life was significantly improved. Conclusion Microsurgical total resection is the key of the treatment. It is an alternative treatment of human malignant gliomas in the safe and effective way that the local chemotherapy of intracerebral implantation of 5-Fu biodegradable polymers combined with local sensitivity radiotherapy of interstitial implantation of 125Ⅰ after microsurgical resection.