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Background. Increasing research is available verifying that asthma is a familial and hereditary disorder of a complex of factors and genes. Objective. To investigate the single and combined associations of five single nucleotide polymorphism loci in three genes with the development of asthma in children of Chinese Han Nationality. Methods. A total of 192 children with asthma and an equal number of control subjects were recruited in this study. Asthma was diagnosed in accordance with American Thoracic Society criteria. Polymerase chain reaction-restriction fragment length polymorphism was used to detect the genotypes of the single nucleotide polymorphism loci. Results. No statistic differences (p > 0.05) were found between experimental and control group in genotype distribution among three loci (NOS1 C5266T, TGF-beta1 L10P, and TGF-beta1 R25P). However, a significant diversity was observed among IL4-RA Q551R (p = 0.004) and TGF-beta1 C-509T (p = 0.000). Furthermore, the frequency of IL4-RA Q551R A/G and TGF-beta1 C-509T C/T in the asthma group were significantly higher than those in the control group (OR = 1.91, P = 0.002; OR = 2.90, P = 0.000, respectively). The carriers of both IL4-RA Q551R A/G and TGF-beta1 C-509T C/T did not have a more significant risk of having asthma than those who covered either. Conclusion. The three loci (NOS1 C5266T, TGF-beta1 L10P and TGF-beta1 R25P) have little contribution to the development of childhood asthma in Chinese Han Nationality. IL4-RA Q551R and TGF-beta1 C-509T are single nucleotide polymorphism loci with significant association to childhood asthma, but they do not have synergistic effects. [ABSTRACT FROM AUTHOR]