Objective: To investigate the value of serum vascular endothelial growth factor (S-VEGF) concentrations in head and neck squamous cell carcinoma (HNSCC). Methods: The sera were obtained from 20 healthy volunteers, 20 patients with head and neck benign tumor (HNBT) and 60 patients with HNSCC. Enzyme-linked immunosorbent assay (ELISA) was performed to measure the concentrations of serum (S) –VEGF. Results: The mean S-VEGF concentrations were 108.8 pg/mL for healthy volunteers, 119.5 pg/mL for patients with HNBT, 261.1 pg/ML for patients with HNSCC. The mean S-VEGF level in patients with HNSCC was significantly higher than in either patients with HNBT or healthy volunteers (P < 0.01). High S-VEGF was associated with lymph node metastasis and larger size of primary tumor. There is a statistical difference between the postoperative (115.3 pg/mL) and the preoperative S-VEGF level (261.1 pg/mL) for HNSCC. Levels of S-VEGF in patients with local recurrence and metastasis were much higher at 237.5 pg/mL and 436.2 pg/mL, respectively. Conclusions: A high S-VEGF level might be associated with poor prognosis in HNSCC.