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Background: Angiogenesis has been shown to be increased in various human tumors including head and neck squamous cell carcinoma (SCC). Vascular endothelial growth factor (VEGF) is thought to be one of the most important angiogenic factors in tumorigenesis. In this study, we aimed to investigate whether polymorphism of VEGF-1154 (A/G) genotypes are associated with the risk of laryngeal SCC. Methods: A prospective, randomized, case-control study in a tertiary university hospital was done. The study group consisted of 57 Caucasian patients with laryngeal SCC and 89 control subjects. Blood samples were obtained before surgery or from the patients under follow-up to 5 years after surgery. VEGF-1154 (A/G) genotypes were detected by real-time polymerase chain reaction with thermal cycler system. Results: According to the high-risk (GG) genotype, the difference between the patient and control groups was statistically significant (OR 0.43, 95% CI = 0.19–0.95, p = 0.037). Conclusions: GG genotype of the VEGF gene may increase the risk of laryngeal SCC in this population. VEGF gene polymorphism may be an important potential genetic and therapeutic marker of laryngeal SCC. [Copyright &y& Elsevier]