In order to investigate the effect of remifentanil combined with propofol on awakening of craniotomy for tumor, a retrospective analysis is conducted. 86 patients who underwent craniotomy for brain tumor in our hospital from July 2020 to December 2021 are chosen to observe the quality of awakening, hemodynamic parameters, and the occurrence of adverse reactions. All patients are divided into group A (n = 43) and group B (n = 43) according to the use of anesthesia drugs. The intraoperative awakening quality and the hemodynamic parameters during different periods of the two groups are compared. The experimental results show that the incidence of postoperative adverse reactions in group B is significantly lower than that in group A (P < 0.05). It is clearly evident that remifentanil combined with protocol has good intraoperative wake-up effect in craniotomy for tumor and maintain the hemodynamic stability of patients. Also, it can obtain high wake-up quality and effectively reduce postoperative adverse reactions.