Epithelioid hemangioma is an uncommon benign vascular lesion with distinct clinicopathological characteristics. Histologically, this entity mainly composed of well-formed but often immature vessels lined by epithelioid endothelial cells with prominent chronic inflammatory component. There is considerable controversy whether epithelioid hemangioma is a reactive lesion or a true neoplasm. We postulated that the local hypoxia may play a role in the pathogenesis of this vascular tumor. This local hypoxic condition may caused by many incidences such as congenital vascular malformation or trauma. The hypoxia will lead to the proliferation of endothelial cells and the formation of this vascular tumor, which may lead by putative stimulators VEGF and HIF-1. Hypoxia may also promote endothelial cell proliferation through the renin-angiotensin-aldosterone system. Additionally, the inflammatory cells including eosinophils and mast cells may contribute to the endothelial cell proliferation in EH. Further study investigating the associated factors of hypoxia may lead to new, potentially important insights into epithelioid hemangioma, and might also contribute to novel strategies for the management of this entity.