Three single nucleotide polymorphisms (SNPs) of the DNMT3B promoter region, C46359T (-149C>T), -283T>C, and -579G>T might be a cancer susceptible factor for several cancers. In this study, we genotyped 226 head-and-neck squamous-cell carcinoma (HNSCC) patients and 249 controls to examine the association between three SNPs of the DNMT3B promoter and the associated risk of the development and/or metastasizing tendency of HNSCC for the population of Taiwan. We observed that only the T/T genotype (C46359T) was found to be present in both patient and control groups (100% frequency). The alleles frequency of -283CC, -283CT and -283TT among patients and controls was, respectively, 88.1% versus 84.3%, 11.9% versus 15.3%, and 0% versus 0.4%. The allele -597GG was not found in both groups, whereas the allele frequency of -597TT and -597GT for patients and controls was, respectively, 88.1% versus 85.5%, and 11.9% versus 14.5%. For both DNMT3B SNPs, inter-group comparison of the allele frequency between patients and controls and distribution of SNPs among cancer patients either featuring or not featuring cervical metastasis did not reveal any significant difference. In conclusion, the relative distribution of three DNMT3B SNPs among a Taiwanese population can not be used as a stratification marker to predict either an individual's susceptibility to HNSCC and/or the likelihood of cervical metastasis of HNSCC.