Aim. To evaluate the possible association between the vitamin D receptor (VDR), single-nucleotide polymorphisms (SNPs), and hepatocellular carcinoma (HCC) in patients with chronic hepatitis B virus (HBV) infection. Method. 968 chronic HBV infection patients were enrolled, of which 436 patients were diagnosed HCC patients, and 532 were non-HCC patients. The clinicopathological characteristics of HCC were evaluated. The genotypes of VDR gene at FokI, BsmI, ApaI, and TaqI were determined. Results. The genotype frequencies of VDR FokI C>T polymorphism were significantly different between HCC and non-HCC groups. HCC patients had a higher prevalence of FokI TT genotype than non-HCC subjects. With FokI CC as reference, the TT carriage had a significantly higher risk for development of HCC after adjustments with age, sex, HBV infection time, α-fetoprotein, smoking status, and alcohol intake. In addition, we also found that the TT genotype carriage of FokI polymorphisms were associated with advanced tumor stage, presence of cirrhosis, and lymph node metastasis. The SNP at BsmI, ApaI, and TaqI did not show positive association with the risk and clinicopathological features of HCC. Conclusion. The FokI C>T polymorphisms may be used as a molecular marker to predict the risk and to evaluate the disease severity of HCC in those infected with HBV.