Objective To explore the efficacy of neuroendoscopy-assisted surgery in the treatment of spontaneous cerebral hemorrhage and its influence on postoperative inflammatory factors and quality of life. Methods: 110 patients with spontaneous cerebral hemorrhage admitted to our hospital from January 2022 to May 2024 were selected as the research subjects. The patients were divided into the open surgery group and the neuroendoscopy group by random number table method, with 55 cases in each group. The open surgery group underwent traditional craniotomy for hematoma evacuation. The neuroendoscopy group underwent hematoma evacuation surgery assisted by neuroendoscopy. The surgical-related indicators (bone window diameter, incision length, intraoperative blood loss, operation time and hematoma clearance rate), occurrence of complications, duration of cerebral edema and neurological dysfunction [National Institutes of Health Stroke Scale (NIHSS)], levels of inflammatory factors (procalcitonin, C-reactive protein), prognosis [Glasgow Outcome Scale (GOS)] and quality of life [SF-36(short form 36 questionnaire) [SF-36)] of the two groups were analyzed and compared. Results: The bone window diameter, incision length, intraoperative blood loss and operation time in the neuroendoscopy group were significantly lower than those in the open surgery group, and the hematoma clearance rate 1 day after the operation was significantly higher than that in the open surgery group (P < 0.05). The incidence of complications in the neuroendoscopy group was significantly lower than that in the open surgery group (P < 0.05). The duration of cerebral edema in the neuroendoscopy group was significantly shorter than that in the open surgery group (P < 0.05). Three weeks after the operation, the NIHSS scores of both groups were significantly lower than those before the operation, and the NIHSS score of the neuroendoscopy group was significantly lower than that of the open surgery group (P < 0.05). Three days after the operation, the levels of procalcitonin and C-reactive protein in both groups increased significantly, but the levels of procalcitonin and C-reactive protein in the neuroendoscopy group were significantly lower than those in the open surgery group (P > 0.05). One year after the operation, the GOS and SF-36 scores of the neuroendoscopy group were significantly higher than those of the open surgery group (P > 0.05). Conclusion: Surgical treatment of spontaneous cerebral hemorrhage assisted by neuroendoscopy can reduce surgical trauma, improve surgical efficacy, lower the incidence of inflammatory responses and complications, promote the recovery of neurological function, and improve the prognosis and quality of life of patients.