Vascular endothelial growth factor (VEGF) is a major regulator of angiogenesis in the process of tumor growth and metastasis. Different VEGF gene polymorphisms have been shown to result in different VEGF protein expression in cancer cells and tumor angiogenic activity. We conducted a case-control study to evaluate the genetic effects of VEGF-460C/T polymorphism on the development of lung cancer. One hundred and twenty-six lung cancer patients and 160 sex-, age-, and ethnic-matched healthy controls were recruited for this study. The genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Odds ratios (ORs) and 95 % confidence intervals (CI) were calculated by logistic regression analysis. Our study showed that the TT genotype was associated with increased lung cancer risk than those with the CC (OR = 1.99, 95 % CI 1.05-3.77) or CT/CC (OR = 1.89, 95 % CI 1.17-3.06) genotype. Moreover, it was observed that the TT genotype associated with the advanced stage among lung cancer patients (TT vs. CC: OR = 3.09, 95 % CI 1.10-8.66). More studies are needed to detect VEGF-460C/T polymorphism and its association with lung cancer in different ethnic populations incorporated with environmental exposures.