Polymorphism of vascular endothelial growth factor (VEGF) influences the VEGF responsiveness and is implicated in various types of diseases with a putative angiogenic basis, but its role in nasopharyngeal carcinoma (NPC) is not fully understood. In this report, we sought to investigate whether the VEGF-2578C/A polymorphism was associated with NPC in a Chinese population. We carried out polymerase chain reaction-restriction fragment length polymorphism in blood genomic DNA of 156 NPC patients and 161 control subjects. The VEGF-2578A allele carriers were significantly associated with an increased risk of NPC (odds ratio: 1.648; 95% confidence interval: 1.053-2.580; P = 0.029). In contrast, NPC patients with the -2578CC genotype were shown higher tumor aggressiveness of large tumor size, poor differentiation and advanced stage as compared to the -2578A allele carriers. No correlation was observed between the genotype or allele distribution and lymph node metastasis or family history of cancer. The VEGF-2578C/A polymorphism was shown to be inconsistent with the onset and aggressiveness of NPC. The precise mechanisms of the polymorphism on the differing status in NPC should be elucidated in further studies.