CD14 is responsible for environmental lipopolysaccharide recognition and is a positional candidate gene for allergy. We hypothesized that genetic polymorphisms in the promoter region of the CD14 gene may be associated with Dermatophagoides pteronysinnus (Der p) allergen sensitization in children. Three single nucleotide polymorphisms (SNPs) of the CD14 promoter region, C(-159)T, A(-1,145)G, and G(-1,359)T were genotyped, and analyzed in 240 randomized case-control school-age children in Taiwan. Serum concentrations of IgE and soluble CD14 (sCD14) were also assayed. We found a significant inverse correlation of sCD14 and total serum IgE levels in our study population. Moreover, sCD14 binds Der p allergen in vitro in a dose-dependent manner. The distribution of three SNPs genotypes was similar in asthmatic children and the control group. However, there was a significant difference in the distribution of genotype CD14 G(-1,359)T, but not C(-159)T, between mite-sensitive and non-sensitive children. Haplotype analysis showed strong linkage disequilibrium among these three SNPs in the CD14 promoter region. Carriers of the CD14-159C/-1,145A/-1,359T haplotype had the highest IgE and lowest sCD14 levels as compared to other haplotypes. Our results support the hypothesis that CD14 gene variants may play an important role in influencing allergen sensitization of children in Taiwan.