OBJECTIVE： To explore the clinical efficacy and safety of nalmefene combined with monosialotetrahexosylganglioside sodium in the treatment of patients in brain tumor operation. METHODS： 64 patients in brain tumor operation were randomly divided into observation group and control group， 32 cases in each group. Control group received brain cell protection， reducing intracranial pressure， anti-infective， vasodilator and other conventional treatment； observation group additionally received 0.7 μg/（kg·h） nalmefene combined with 100 mg/d monosialotetrahexosylganglioside sodium from the first day of operation， for continuous 7 d. The plasma cortisol， adrenocorticotropic hormone （ACTH） before and 3， 7 d after treatment， changes of serum IL-6， TNF-α and Barthel index （BI） in 2 groups were observed， improvement of neurological function and ADR were observed； Karnofsky （KPS） score was determined after 90 d follow-up used to assess the patient’s ability to take care of themselves. RESULTS： After treatment， plasma cortisol and ACTH content， serum TNF-α and IL-6 levels in 2 groups significantly decreased than before， the difference was statistically significant （P＜0.05）； cortisol， ACTH and TNF-α levels 3， 7 d after treatment， IL-6 level 7 d after treatment in observation group decreased more significantly than control group， the differences were statistically significant （P＜0.05）. After treatment， BI score in 2 groups significantly increased， and observation group increased more significantly than control group， the differences were statistically significant （P＜0.05）. 7 d after treatment， improvement rate of neurological function was 50.00％， which was significantly higher than that of the control group （18.75％）， the difference was statistically significant （P＜0.05）. There was no significant ADR occurred of 2 groups in the study. Following-up for 90 d， the KPS score in observation group with not less than 70 points accounted for 71.88％， which was significantly higher than the control group （46.87％）， the difference was statistically significant （P＜0.05）. CONCLUSIONS： Nalmefene combined with monosialotetrahexosylganglioside sodium can promote the recovery of patients in brain tumor operation， reduce cortisol， ACTH， IL-6 and TNF-α levels and improve prognosis of patients.