**Abstract**

Tumor angiogenesis and tumor progression to late oral squamous cell carcinoma are closely related. Vascular endothelial growth factor (VEGF), a heparin-binding growth factor with mitogenic activity specific for vascular endothelial cells, regulates key events of the pathological angiogenesis involved in the metabolic functions of malignant tissues. The level of high-affinity tyrosine kinase receptor for VEGF, *flt*, in tumor endothelial cells *in vivo* is seen upregulated, supporting the role of VEGF as a potential signaling tumor angiogenesis axis *in vivo* and sustaining the notion that paracrine mechanisms are responsible for the regulation of tumor angiogenesis. The expression of VEGFs is increased in the processes of oral squamous cell carcinoma (OSCC) progression and proliferation. Vascular endothelial growth factor C (VEGF-C)/VEGF3 expression induced by chemokine CCL4 is connected to lymph node metastasis in OSCC. This chapter was aimed to summarize and analyze the findings on the role of vascular endothelial growth factor in oral squamous cell carcinoma and briefly discuss the potential of vascular endothelial growth factor that targets this pathway as treatment for OSCC.

**Keywords:** angiogenesis, vascular endothelial growth factor, oral cancer, overexpression, VEGF polymorphism
