AIM: To investigate the correlation between C/T single nucleotide polymorphism (SNP) in the promoter of the DNA methyltransferase 3B (DNMT3B) gene and risk for development and progression of primary hepatocellular carcinoma (HCC).METHODS: One hundred case subjects were selected consecutively from Tongji Hospital (Wuhan, China).from March to November 2006. They did not receive radiotherapy or chemotherapy for newly diagnosed and histopathologically confirmed HCC. One hundred and forty control subjects having no history of cancerous or genetic diseases were healthy volunteers to Wuhan Blood Center in the same period. Frequency was matched for sex, age, alcohol consumption and cigarette smoking status of the case subjects. C/T polymorphism of the DNMT3B promoter was analyzed using polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) and sequencing analysis. The association between genotypes of DNMT3B and clinicopathological parameters among cases was also studied.RESULTS: The CC genotype was not detected in both HCC patients and controls. In control ubjects, the frequency of TT and CT genotypes was 99.3% and 0.7%respectively, and that of T and C alleles was 99.6%and 0.4% respectively. The frequency of CT genotype was higher in HCC (3.0%). The frequency of T and C alleles was 98.5% and 1.5% respectively. However, the genotype and allelotype distribution in HCC patients was not significantly different from that in controls.CONCLUSION: C/T polymorphism is not associated with the increased risk of HCC. DNMT3B enetic polymorphism is variable in different races, ethnic groups or geographic areas. Further study is needed to clarify the role of DNMT3B SNP in the development of HCC among other populations.