The aim of the present study was to confirm the association between the CD14-159C/T polymorphism and tuberculosis in the Korean population and to elucidate the functional basis for this putative association. CD14-159C/T genotypes were determined by PCR - restriction fragment length polymorphism analysis in 274 tuberculosis patients and 422 healthy controls. Recombinant CD14 promoter-luciferase reporter constructs, including the -159T or -159C allele, were transfected into K562 and BEAS-2B cells, and luciferase activities were measured and compared. Levels of serum sCD14 and interferon-gamma secreted by peripheral blood mononuclear cells (PBMCs) were measured using enzyme-linked immunosorbent assay.The frequency of -159TT genotypes was higher in tuberculosis patients than in healthy controls. The promoter activity of the -159T allele was higher than that of the -159C allele. Serum sCD14 levels were higher among tuberculosis patients with -159TT genotypes than among those with -159CC genotypes and interferon-gamma release by PBMCs was decreased in subjects with -159TT genotypes. In conclusion, the -159TT CD14 genotypes were associated with tuberculosis development in Koreans. This association might be a result of the higher promoter activity of the -159T allele, the higher level of sCD14, and the decreased interferon-gamma secretion in subjects with -159TT genotypes.