The vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogen involved in the process of angiogenesis, a crucial phase in tumor growth and metastasis. We carried out a case-control study to evaluate whether VEGF -2578C/A gene polymorphism modulates the risk of developing colon cancer. A total of 110 colon cancer patients and 110 cancer-free healthy people were recruited in the Chinese population. Genomic DNA was isolated from peripheral blood, and gene polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism. Colon cancer patients had a significantly higher frequency of VEGF -2578AA genotype (odds ratio=2.49; 95% confidence interval=1.04, 6.01; p=0.04) than controls. Patients with left colon cancer had a significantly higher frequency of VEGF -2578AA genotype (odds ratio=2.31; 95% confidence interval=1.03, 5.18; p=0.04) than those with right colon cancer. When stratified by tumor size, growth pattern, differentiation, and stage of colon cancer, no statistically significant results were observed. This study suggested that VEGF -2578AA genotype was associated with a higher risk of colon cancer in Chinese population. Further studies are needed to understand the mechanism of VEGF gene polymorphisms in the development and progression of colon cancer.