AIM: To elucidate the relationship between childhood asthma susceptibility and clinical efficacy of inhaled glucocorticoids (ICS) in children with different genotypes of asthma by exploring rs776746 and rs15524 single nucleotide polymorphisms (SNPs) of cytochrome P450 enzyme 3A5 (CYP3A5) gene in asthmatic children and healthy children. METHODS: The CYP3A5 gene rs776746 and rs15524 polymorphic sites were detected in 79 children (Case group) with asthma of Han nationality and 100 healthy children (Control group) who met the inclusion criteria admitted to the Northern Theater General Hospital in Northeast China from October 2016 to October 2020, and genotype, allele and linkage analysis were performed. The case group was given inhaled glucocorticoids by nebulised inhalation for 3 months, and lung function and exhaled breath nitric oxide (FeNO) were measured at entry and after treatment, and asthma control score C-ACT/ACT was done after treatment, so as to compare the prevalence of different genotypes and the differences in the above test index scores. RESULTS: There was complete linkage disequilibrium at rs776746 and rs15524 loci. There were three genotypes of T/T, T/C and C/C at rs776746 locus of CYP3A5 gene. There were significant differences in the frequency of different genotypes between the case group and the control group (c2=9.121, P=0.010). The probability of asthma in T/C genotype was 6.345 times higher than that in T/T genotype (P=0.007), that in C/C genotype was 3.864 times higher than that in T/T genotype (P= 0.044), and that in variant type was 4.682 times higher than that in wild-type (P=0.011); There were three genotypes of A/A, A/G and G/G at rs15524 locus. There were significant differences in the frequency of different genotypes between the case group and the control group (c2=9.121, P=0.010). The probability of asthma of genotype A/A was 3.864 times higher than that of genotype G/G (P=0.044), and the probability of asthma of genotype A/G was 6.345 times higher than that of genotype G/G (P=0.007). When comparing the frequency of G/G and A/A+A/G in the case group and the control group, it was found that the probability of asthma of the latter was 4.682 times higher than that of the former (P=0.011). The improvement rate of the measured value of FEF50 and FEF75 at rs776746 was significantly higher than that of wild type (t=-2.499, -3.256, P=0.024, 0.019), and the improvement rate of the measured value of FEF50 and FEF75 at rs15524 was significantly lower than that of wild-type (t=3.380, 2.325, P=0.015, 0.042). The C-ACT/ACT score of rs776746 locus variant was significantly higher than that of wild-type group (t=0.571, P=0.037); There was no significant difference between wild-type and variant C-ACT/ACT scores at rs15524 locus (t=0.486, P=0.545). CONCLUSION: The rs776746 and rs15524 loci of CYP3A5 gene are the susceptibility loci of childhood asthma. The wild-type or variant of rs776746 and rs15524 loci are related to the improvement of small airway function after inhaled ICs treatment. Wild type or variant of rs776746 locus also affected asthma control.