Abstract: Objective To investigate the effect of ulinastatin combined with dexmedetomidine on oxidative stress, S100β and NSE in patients with supratentorial tumor resection. Methods A total of 60 patients with supratentorial tumor resection were randomly divided into observation group (30 cases) and control group (30 cases). The patients of the control group received ulinastatin (2 000 U/kg) at time of skin incision, then received dose of 1 000 U/(kg·h) until the end of the operation. On the basis of control group, the patients of observation group received dexmedetomidine at the same time, dose of 1 μg/kg at time of skin incision, then received dose of 0.5 μg/(kg·h) until 30 min before the end of the operation. SOD, MDA, S100β and NSE of jugular venous bulb serum were tested and compared in 2 groups at the time of before induction (T0), before skin incision, after cutting epidural, end of operation and 24 h after operation. Results Compared with T0, the level of SOD decreased significantly at T2, T3 and T4 in 2 groups (P<0.05), the level of MDA increased significantly at T2, T3 and T4 in 2 groups (P<0.05), but the changes of observation group was significant smaller (P<0.05). Compared with T0, the level of S100β and NSE increased significantly at T2, T3 and T4 in2 groups (P<0.05), but the changes of observation group was significant smaller (P<0.05). Conclusion Ulinastatin combined with dexmedetomidine can obviously reduce the inhibition of SOD, MDA level and oxidative stress damage.At the same time, reduce S100βand NSE, boost brain protection in patients with supratentorial tumor resection.