Objective: To compare the effects of propofol and dexmedetomidine sedation on renal function in patients with intracranial hemorrhage (ICH), and to explore the related mechanism. Methods: A total of 80 patients with ICH admitted to the intensive care unit (ICU) of the Second Hospital of Anhui Medical University from January 2020 to December 2021 were selected and randomly divided into a propofol sedation group (Group P) and a dexmedetomidine sedation group (Group D), each group with 40 patients. The patients in the Group P received a loading dose of 1 mg/kg propofol within 15 min, followed by sedation with a propofol maintenance dose of 1–3 mg/(kg·h); The patients in the Group D received a loading dose of 1.5 μg/kg dexmedetomidine within 15 min, followed by sedation with a dexmedetomidine maintenance dose of 0.6 μg/(kg·h); The general information of all patients was recorded. Before sedative drugs administration (T0), 12 h after administration (T1) and 24 h after administration (T2), the levels of plasma interleukin-6, procalcitonin and blood creatinine were measured by enzyme-linked immunosorbent assay (ELISA). Results: Compared with T0, the expression levels of interleukin-6, procalcitonin and blood creatinine in the 2 groups significantly increased at T1 and T2 time points. There was no difference in the expression levels of interleukin-6 and procalcitonin between the 2 groups at T1 and T2. At T1 and T2 time points, the expression level of blood creatinine in Group P was significantly higher than that in Group D. Conclusion: Compared with propofol sedation, dexmedetomidine sedation can significantly reduce the level of serum creatinine and protect renal function in patients with intracranial hemorrhage. This effect is not related to the regulatory effect of the two drugs on systemic inflammatory response.