Objective: To investigate the relationship between vascular endothelial growth factor (VEGF), endothelial cell proliferation and angiogenesis in human hemangioma using immunohistochemical staining techniques. Methods: Immunohistochemical staining techniques are used to show the VEGF proliferating cell nuclear antigen (PCNA) and CD34 expression, respectively, in 54 patients with hemangioma and 15 samples of normal skin and mucosa from the oral and maxillofacial region. Quantitation of VEGF-PCNA expression and microvascular density (MVD) are also performed. Results: The concentration of VEGF and PCNA protein decreased during the three phases (proliferating, involuting and involuted phase) in human hemangioma samples and was negatively expressed in normal tissues. The expression of VEGF had close relationship with proliferation of hemangioma endothelial cells (P < 0.05). The MVD did not have notable difference between proliferating and involuting phase, but had significant difference between proliferating and involuted phase. The expression of VEGF had a sound relationship with angiogenesis in human hemangioma. Conclusion: VEGF is associated with endothelial cells proliferation and angiogenesis in human hemangioma. It may be the key regulator in the etiology of hemangioma.