Objective To investigate the efficacy of urokinase combined with endoscopic hematoma clearance in patients with supratentorial hypertensive intracerebral hemorrhage and its effect on the expression of serum high-mobility group box-1 （HMGB-1） and tumor necrosis factor-related apoptosis-inducing ligand （TRAIL）.Methods A total of 110 patients with supratentorial hypertensive cerebral hemorrhage who were admitted to our hospital from August 2018 to June 2020 were enrolled， and according to the treatment regimen， they were divided into control group and observation group， with 55 patients in each group. The patients in the control group were given conventional treatment and endoscopic hematoma clearance， and those in the observation group were given urokinase flushing in addition to the treatment in the control group. The two groups were compared in terms of National Institutes of Health Stroke Scale （NIHSS） score， local cerebral blood flow， serum inflammatory factors， clinical outcome， and the expression of serum HMGB-1 and TRAIL before and after treatment.Results After treatment， the observation group had a significantly higher overall response rate than the control group （P <0.05）. Compared with the control group， the observation group had a significantly higher cerebral blood flow in the far and near areas （P <0.05）. The observation group had a significantly lower NIHSS score than the control group （P <0.05）. Compared with the control group， the observation group had significantly lower serum levels of high-sensitivity C-reactive protein， interleukin-6， tumor necrosis factor-α， HMGB-1， and TRAIL （P <0.05）.Conclusions Urokinase combined with endoscopic hematoma clearance is effective in patients with supratentorial hypertensive intracerebral hemorrhage and can inhibit the expression of HMGB-1 and TRAIL， effectively improve local cerebral blood flow， and reduce the serum levels of inflammatory factors.