Objective:To investigate the expression of vascular endothelial growth factor (VEGF) in oral squamous cell carcinoma by serum-starvation and hypoxia. Methods:The expression of VEGF mRNA was evaluated in two oral squamous cell carcinomas cells TSCCa and GNM treated with serum-starvation and hypoxia.using semi-quantitative RT-PCR. The activities of VEGF in two cell lines were detected by enzyme linked immunosorbent assay (ELISA). Results:Contrast to TSCCa cells, GNM cells expressed significantly higher levels of mRNA of VEGF by RT-PCR detection. Serum-starvation and hypoxia could increased expression of VEGF mRNA in both two cell lines in vitro, the levels of mRNA of VEGF increased more in TSCCa cell lines than that in GNM cell lines when treated with serum-starvation and hypoxic. After 4 hours hypoxic treatment, the activities of VEGF increased significantly and approached the peak after 8 hours; the activities of VEGF in GNM cell lines was dramatically twice higher than that of the control group, while the activities of VEGF increased by 6 times in TSCCa cell lines. The activities of VEGF in TSCCa cell lines were higher than that of in GNM cell lines when treated with serum-starvation. Conclusion: Serum-starvation and hypoxia can up-regulate VEGF mRNA expression and activities in oral squamous cell lines in vitro,which may play an important role in the angiogenesis of oral squamous cell carcinoma.