Objective To investigate the effect of stereotactic guided hematoma puncture drainage combined with urokinase on moderate hypertensive cerebral hemorrhage. Methods A total of 230 patients with moderate hypertensive intracerebral hemorrhage admitted from June 2014 to June 2020 were selected and randomly divided into two groups, 115 cases in each group. The control group was treated by traditional craniotomy and the observation group was treated with urokinase. Residual hematoma, Glasgow outcome score （GOS）, inflammatory factors, complication rate were compared between the two groups after 7 days of designed treatment and 3 months of follow-up. Results The observation group showed less amount of residual hematoma 3 and 7 days after operation, and a higher GOS score 3 months after operation that the control group did （P<0.05）. The inflammatory factors 7 days after operation in both groups were lower than those before operation （P<0.05）. After 7 days of operation, the levels of NSE, IL-6, S100β, and TNF-α in the observation group were lower than those in the control group （P<0.05）. Cox survival curve analysis revealed that the prognosis of patients with moderate hypertensive intracerebral hemorrhage was related with blood loss and consciousness at admission awareness （P<0.05）, but not with age and gender （P>0.05）. The incidence of complications in the observation group within 3 months after surgery （4.00%） was lower than that in the control group （16.00%, P<0.05）. Conclusion Stereotactic guided hematoma puncture and drainage combined with urokinase therapy for moderately hypertensive intracerebral hemorrhage patients can effectively remove hematoma, improve prognosis, and reduce the incidence of complications.