To explore the association of a disintegrin and metalloprotease 33 (ADAM33) polymorphisms with childhood asthma susceptibility, we conducted this case-control study.In this case-control study, we selected 96 asthma children and 86 healthy children to conduct the genotyping of ADAM33 polymorphisms through polymerase chain reaction-direct sequencing (PCR-DS). Hardy-Weinberg equilibrium (HWE) status in the control group was detected adopting chi-square test. Frequency differences of genotypes, alleles, and haplotypes were compared by chi-square test between the case and control groups. Linkage disequilibrium (LD) between polymorphisms was checked using Haploview software. Association intensity of the polymorphisms with the disease risk was assessed by odds ratio (OR) and 95% confidence interval (95%CI).The frequency of rs678881 GA genotype was obviously higher in cases than in controls (P = .03) and the carriage of this genotype conferred higher risk of asthma among children than GG genotype (OR = 2.03, 95%CI = 1.05-3.91). However, neither rs2280089 nor rs2853209 polymorphism was significantly associated with the risk of childhood asthma. Strong LD was found among rs678881, rs2280089 and rs2853209, and haplotype GGT was distinctly associated with the risk of asthma in children (OR = 0.28, 95%CI = 0.13-0.57).ADAM33 rs678881 polymorphism is significantly correlated with increased susceptibility to asthma in Chinese Han children. Besides, haplotype GGT among the 3 polymorphisms was obviously associated with decreased risk of childhood asthma.