The -159C/T polymorphism in the CD14 gene has been implicated in susceptibility to asthma, but a large number of studies have reported inconclusive results. The aim of this study is to investigate the association between the -159C/T polymorphism in the CD14 gene and the risk of asthma by meta-analysis. We searched Pubmed, Embase, CNKI database, Wanfang database, Weipu database, and Chinese Biomedical database, covering all publications (last search been performed on April 20, 2010). Statistical analysis was performed by using the softwares Revman 4.2 and STATA 10.0. A total of 17 case-control studies in 17 articles (4,246 cases and 3,631 controls) were included in this meta-analysis. There was no association between this polymorphism and asthma risk in combined analyses (odds ratio (OR) = 0.86 and 95% confidence interval (95% CI) = 0.72-1.02, P = 0.09 for TC + TT vs. CC). In the subgroup analysis by age, ethnicity, and atopic status, no significant associations of asthma risks were obtained from age groups, ethnic groups, and atopic groups for TC + TT vs. CC comparison. For atopic population, significant decreased atopic asthma risks were found among Asian population (OR = 0.69, 95% CI 0.52-0.92, P = 0.01) and children population (OR = 0.69, 95% CI 0.54-0.89, P = 0.0004) for TC + TT vs. CC comparison. This meta-analysis suggests that CD14 is a candidate gene for atopic asthma susceptibility. The -159C/T polymorphism may be a protective factor for atopic asthma in Asian and children. More studies are needed to validate these associations.