Abstract： Objective： To observe the effect of Qingre Sanyu Jiedu Prescription combined with hypothermia therapy on central hyperthermia caused by severe craniocerebral injury （SCI）. Methods： Ninety SCI patients with central hyperthermia hospitalized at Henan Province Hospital of Traditional Chinese Medicine from May 2022 to May 2025 were selected and randomly divided into the combination group and the control group using the random number table method， with 45 cases in each group. The control group was treated with a hypothermia therapy apparatus. The combination group received additional treatment with Qingre Sanyu Jiedu Prescription enema based on the control group's regimen. Changes in body temperature， neurological deficits [European Stroke Scale （ESS）， Glasgow Coma Scale （GCS）]， inflammatory factors [interleukin-6 （IL-6）， C-reactive protein （CRP）， tumor necrosis factor- α（ TNF-α）]，systolic blood pressure（ SBP），diastolic blood pressure（ DBP），clinical efficacy，and the incidence of adverse events were compared between the two groups. Results： After treatment， the total effective rate was 95.56% （43/45） in the combination group and 82.22% （37/45） in the control group，showing a statistically significant difference （P＜0.05）. After 48 hours of treatment， body temperature decreased in both groups compared to before treatment （P＜0.05），and the body temperature in the combination group was lower than that in the control group （P＜ 0.05）. After treatment，ESS and GCS scores increased in both groups compared to before treatment （P＜0.05）；and the ESS and GCS scores in the combination group were higher than those in the control group （P＜0.05）. After treatment，the levels of IL-6，CRP，and TNF-α decreased in both groups compared to before treatment （P＜0.05）； and the levels of IL-6，CRP，and TNF-α in the combination group were lower than those in the control group （P＜ 0.05）. After treatment，SBP and DBP levels decreased in both groups compared to before treatment （P＜0.05）；and the SBP and DBP levels in the combination group were lower than those in the control group （P＜0.05）. The incidence of adverse events was 8.89% （4/45） in the combination group and 15.56% （7/45） in the control group， with no statistically significant difference between the two groups （P＞0.05）. Conclusion： Qingre Sanyu Jiedu Prescription enema combined with hypothermia therapy for central hyperthermia caused by SCI can effectively reduce the inflammatory response， lower body temperature， improve neurological function， delay disease progression， and no adverse events will be increased in the short term.