| Objective: To compare the effects of minimally invasive drilling drainage and urokinase on intracranial blood clot lysis in patients with cerebral hemorrhage. Methods: From April 2018 to April 2019, 84 patients with cerebral hemorrhage were selected and divided into two groups. The study group was treated with minimally invasive drilling drainage, while the control group was treated with urokinase. The effect of intracranial blood clot dissolution was recorded. Results: After treatment, the total effective rate of the study group was significantly higher than that of the control group (P < 0.05). After treatment, the hematoma clearance rate in the study group was significantly higher than that in the control group (P < 0.05). After treatment, the serum GFAP content in both groups was significantly lower than that before treatment, and the study group was also significantly lower than that in the control group (P < 0.05). The closure time and drainage time of the study group were significantly less than those of the control group (P < 0.05). Conclusion: Compared with urokinase, the application of minimally invasive drilling drainage in cerebral hemorrhage can promote the dissolution of intracranial blood clots, inhibit the release of serum GFAP, reduce the time of closure and drainage, and thus improve the therapeutic effect.