Objective To compare the anesthetic efficacy and cerebral protective effects of dexmedetomidine (Dex) and propofol-combined anesthesia and the effects thereof on the hemodynamics of patients with brain tumor surgery. Methods From February 2018 to February 2020, 62 patients who underwent elective brain tumor surgery in our hospital, were enrolled and divided into the Dex combined anesthesia group (n?=?31) and the propofol combined anesthesia group (n?=?31) through random number table method, among which there were 37 cases of glioma and 25 cases of meningioma. The heart rate (HR), mean arterial pressure (MAP), central venous oxygen saturation (ScVO2), internal jugular venous oxygen saturation (SjVO2), and neuron-specific enolase (NSE), S100β protein levels of the patients were monitored before anesthesia induction (T0), during dural incision (T1), after tumor removal (T2), at the end of surgery (T3), and 24 hours after surgery (T4).The recovery time, extubation time, observer’s assessment of alertness/sedation (OAA/S) score after extubation and incidence of postoperative adverse reactions were recorded. Results There were differences in HR and MAP between the two groups at different time points (P??0.05). Conclusions Compared with propofol combined anesthesia, Dex combined anesthesia has a better anesthetic and sedative effect on patients undergoing brain tumor surgery, which is conducive to the stability of hemodynamics and brain metabolism, more effective protection of brain tissue and higher safety, and is of great value for clinical application.