Objective To investigate the function and mechanism of epidermal growth factor-like domain 7 (VE-statin/Egfl7) in malignant glioma angiogenesis by cell culture and RNA interference.Methods Interaction between tumor cells and endothelial cells in malignant glioma was simulated by transwell-based co-culture of U251 and HUVEC cells. A lentivirus system carrying siRNA was used to inhibit the expression of VE-statin/Egfl7 in HUVEC cells and U251 cells. The effects of VE-statin/Egfl7 on angiogenesis in malignant glioma microenvironment were evaluated by endothelial cell proliferation, adhesion, migration, and tube formation assay.Results After VE-statin/Egfl7 gene silencing, a temporary growth inhibition was observed in HUVEC cells, followed by immediate recovery of normal proliferation. The endothelial cell migration was not affected, while the adhesion of endothelial cells was significantly inhibited. VE-statin/Egfl7 gene silencing also significantly suppressed the formation of capillary-like structures by endothelial cells. Conclusions VE-statin/Egfl7 plays a key role in the formation of vascular tubular structure in malignant glioma angiogenesis via regulation of endothelial cell adhesion.