Objective To analyze the effects of endovascular interventional therapy on serum neuron-specific enolase (NSE) and S100B protein levels in patients with intracranial microruptured aneurysms. Methods A total of 62 patients with intracranial microrupture aneurysms admitted to the First Affiliated Hospital of Chongqing Medical University from December 2012 to August 2020 were selected and divided into the control group and the observation group by random number table method, with 31 cases in each group. Patients in the control group were treated with craniotomy and clipping, and patients in the observation group were treated with intravascular interventional therapy. Both groups were followed up for 6 months after surgery. The operation-related indicators, aneurysm occlusion degree and prognosis 6 months after operation, NSE and S100B levels before and 1 day after surgery, the complications occurred during the follow-up period were companid between the two groups. Results The operation time and hospital stay of the observation group were significantly shorter than those of the control group; the operation cost was significantly higher than that of the control group; the proportion of patients with dense occlusion in the observation group were significantly higher than that in the control group; 6 months after the operation, the Glasgow Outcome Score (GOS) score of the observation group were significantly higher than that of the control group (all P <0.05); compared with before operation, the serum NSE and S100B protein levels in the two groups increased significantly 1 day after surgery, but there was no statistical significance between the two groups (P >0.05); During the follow-up period, the incidence of complications in the observation group were significantly lower than that in the control group (P <0.05). Conclusion Endovascular interventional therapy for patients with microruptured intracranial aneurysms can shorten operative time and hospital stay, reduce nerve damage, improve the occlusion of aneurysms, it is safe and effective, and then improve patient prognosis.