Objective To investigate the effect of minimally invasive hematoma evacuation with small bone window on vascular endothelial function indexes and inflammatory factors levels in patients with hypertensive cerebral hemorrhage at different time points. Methods A retrospective analysis was performed on the clinical data of 200 patients with hypertensive cerebral hemorrhage admitted to the Zibo Medical Area, 960th Hospital of People's Liberation Army Joint Service Support Force from January 2019 to September 2021, according to the different operation time points, they were divided into the early group and the super early group, 100 cases in each group. Patients in the early group were treated with minimally invasive hematoma evacuation with small bone window within 6~24 hours after onset, patients in the super early group were treated with minimally invasive hematoma evacuation with small bone window within 6 hours after onset, patients in both groups were observed for 6 months after operation. The clinical efficacy 6 months after operation and perioperative indexes of patients in the two groups were compared, the serum levels of interleukin-6 (IL-6), hypersensitive C-reactive protein (hs-CRP), matrix metalloproteinase-9 (MMP-9), endothelin (ET), angiopoietin-1(Ang-1), and vascular endothelial growth factor (VEGF) before and 7 d after operation, and the incidence of complications within 6 months after operation of patients in the two groups were compared. Results 6 months after operation,the total clinical response rate in the super early group was significantly higher than that in the early group, the hospital stay, ambulation time and recovery time of consciousness were significantly shorter than those in the early group, and the amount of intraoperative blood loss was significantly lower than that in the early group; compared with before operation, the serum levels of IL-6, hs-CRP, MMP-9, ET and ANG- 1 of patients in two groups 7 d after operation decreased significantly, and the super early group was significantly lower than the early group, while the serum VEGF level 7 d after operation increased significantly, and the super early group was significantly higher than the early group (all P<0.05); the total incidence of complications in the super early group was lower than that in the early group, but the difference was not statistically significant (P>0.05). Conclusion Compared with minimally invasive hematoma evacuation with small bone window in the early stage, operation in the super early stage can shorten the hospital stay and ambulation time in patients with hypertensive cerebral hemorrhage, improve nerve function, regulate vascular endothelial function, and reduce inflammatory response, and the security is good.