Objective To explore the effects of high intensity focused ultrasound (HIFU) on cell multiplication and apoptosis at exposure coverage and marginal zone and the expression of vascular endothelial growth factor (VEGF) and proliferating cell nuclear antigen and apoptosis of subcutaneous neurogliocytoma in nude mice. Methods Eighteen nude mice bearing subcutaneous human neurogliocytoma were consecutively ablated in 20s by an extracorporeal HIFU with 9.7MHz transducer (the focal length of 4.5mm and focal intensity 2500W/cm2). The 18 nude mice were randomly di?vided into 7 d group,14 d group and 30 d group according to sacrifice date. Immunohistochemical method, TdT-mediat?ed dUTP nick end labeling method were used to examine the expression of vascular endothelial growth factor and prolifer?ating cell nuclear antigen and apoptosis at exposure coverage, marginal zone and normal zone, respectively. Results The expression of VEGF and proliferating cell nuclear antigen were evident at exposure coverage, marginal zone and normal zone in 7, 14 and 30 days after ablation. The expression of proliferating cell nuclear antigen and apoptosis were absent at exposure coverage in 7,14 and 30 days after ablation. The percentage of VEGF expression was lower in marginal zone than in normal zone (23.79%± 3.11% vs. 46.16%± 2.43%) in 7 d after ablation (F=110.03,P<0.05). The percentage of VEGF expression was also lower (10.94%±3.95%) in exposure coverage than in normal zone (46.16%±2.43%) in 7 d af?ter ablation (F=272.80,P<0.05). The percentage of VEGF expression was lower in marginal zone than in normal zone (17.17%±2.89%vs. 43.47%±3.77%) in 14 d after ablation (F=152.05,P<0.05). The percentage of VEGF expression was lower in marginal zone than in normal zone (9.27%± 2.08%vs. 44.58%± 3.34%) in 30 d after ablation (F=274.1,P<0.05 2). The proliferating cell nuclear antigen labeling index(PCNA LI) was lower in marginal zone than in normal zone ((33.04%±4.31%vs. 65.15%±3.85%) in 7 d after ablation (F=242.46, P<0.05). The PCNA LI was lower in marginal zone than in normal zone (21.05%± 1.96%vs. 62.99%± 3.34%) in 14 d after ablation (F=413.52, P<0.05). The PCNA LI was lower in marginal zone than in normal zone (6.36%± 0.51% vs. 62.07%± 18.07%) in 30 d after ablation, (F=729.59, P<0.05) .The apoptotic index (AI) was higher in marginal zone than in normal zone (26.10%±4.54%vs. 1.43%±0.35%) in 7 d after ablation, (F=216.22, P<0.05). The apoptotic index(AI) was higher in marginal zone than in normal zone (65.70%± 1.14% vs. 1.82%± 0.31%) in 14d after ablation (F=1448.64, P<0.05). The apoptotic index (AI) was higher in marginal zone than in normal zone (82.02%± 3.98% vs. 2.52%± 0.29%) in 30d after ablation (F=2244.33, P<0.05). Conclusion The present study demonstrates that an extracorporeal HIFU with 9.7MHz transducer (the focal length of 4.5mm and fo?cal intensity 2500W/cm2) can completely ablate neurogliocytoma at exposure coverage and inhibit the proliferation of neurogliocytoma at marginal zone. Thus, HIFU may be a new and selective treatment for neurogliocytoma.