Objective To investigate the relationship between the polymorphism of loci 589C/T(rs2243250) and 33 C/T(rs2070874) of gene promoter region of interlukin-4 (IL-4) and susceptibility and severity of respiratory syncytial virus (RSV) bronchiolitis and to explore the effects of differences of genetic mechanisms on the incidence and prognosis of RSV infection. Methods Polymorphism of IL-4-589C/T and IL-4-33C/T of 218 patients with RSV bronchiolitis (RSV bronchiolitis group) and 303 healthy controls (control group) were detected by MGB-Taq Man probe method and the severity of RSV bronchiolitis was evaluated by the respiratory scoring system. Results The frequencies of CC, CT and TT genotypes of IL-4-589 of the RSV bronchiolitis group were 1.4%, 21.1%, and 77.5% and those of the control group were 1.7%, 34.0%, and 64.4%, respectively. The differences were statistically significant (P=0.005). The frequencies of all elomorphic genes C and T of IL-4-589 of the RSV bronchiolitis group were 11.9% and 88.1% and those of the control group were 18.6% and 81.4%, respectively. The differences were statistically significant (P=0.003). The frequencies of CC, CT and TT genotypes of IL-4-33 of the RSV bronchiolitis group were 1.4%, 20.6%, and 78.0% and those of the control group were 2.3%, 35.6%, and 62.0%, respectively. The differences of two groups were statistically significant (P=0.001). The frequencies of all elomorphic gene C and T of IL-4-33 of the RSV bronchiolitis group were 11.7% and 88.3% and those of the control group were 20.1% and 79.9%, respectively. The differences were statistically significant (P=0.000). Haplotype analysis found linkage disequilibrium at IL-4-589 and IL-4-33 (D′=0.75). The differences of the frequency of T-T haplotype of IL-4-589 and IL-4-33 of two groups were statistically significant (P=0.000). The clinical respiratory scores of patients with IL-4-589TT in the RSV bronchiolitis group were significantly higher than those of patients with IL-4-589CT (P=0.002). The clinical respiratory scores of patients with IL-4-33TT were significantly higher than those of patients with IL-4-33CT (P=0.001). Conclusion The polymorphism of IL-4-589C/T and IL-4-33C/T was relevant to the susceptibility and severity of RSV bronchiolitis.