Vascular endothelial growth factor (VEGF) is a key mediator of angiogenesis, which is crucial for development and metastasis of tumors including hepatocellular carcinoma (HCC), and elevated VEGF levels in serum and tissues have been known to be related with poor prognosis in patients with HCC. Polymorphisms in VEGF may alter VEGF protein concentrations, influence the process of angiogenesis, and may relate to interindividual variation in tumorigenesis. In this study, we carried out a case-control study in a Chinese population (206 cases and 302 controls) to estimate the susceptibility to HCC associated with an 18-bp insertion/deletion polymorphism (rs35569394) in the promoter region of VEGF. After adjusting the data by gender, age, smoking status, drinking status, and hepatitis B virus (HBV) infection using logistic regression model, we found that rs35569394 was not associated with HCC, at both the allele and genotype levels. Thus, rs35569394 should not be viewed as a major contributor to the development of HCC in Chinese.