ABSTRACT. Asthma is an allergic disease characterized by hyperresponsiveness and chronic inflammation of the airway. The interleukin-4 (IL-4) gene and its single nucleotide polymorphisms are associated with asthma susceptibility in children. A case-control study was performed to evaluate the relationship between asthma risk and the IL-4 rs2243250 (589 C/T) and rs2070874 (107 T/C), and IL-4 receptor (IL-4R) rs1801275 (576 Q/R) polymorphisms in 317 childhood asthma patients and 351 healthy children as controls. Polymerase chain reaction amplification and sequencing was performed. The effects of interactions between the genes of interest and environmental factors were also analyzed. IL-4 rs2243250 and rs2070874 allele and genotype frequencies did not significantly differ between the asthma and control groups (P > 0.05), but those of IL-4R rs1801275 did (P < 0.05). The RR genotype and R allele of this IL-4R variant were significantly associated with asthma risk, with odds ratios (ORs; and 95% confidence intervals) of 2.97 (2.08-4.25) and 2.99 (2.32-3.85), respectively. Logistic regression analysis showed that the IL-4R 576 Q/R RR genotype demonstrated a positive interaction with environments associated with smoking or pets in its effect on asthma risk, with ORs of 2.18 (P = 0.02) and 2.29 (P = 0.01), respectively. Our results suggest that the IL-4R rs1801275 polymorphism is associated with childhood asthma, and the RR genotype confers a high risk of developing this condition. This variant exhibited positive interactions with environments in which smoking or pets were present in increasing the risk of childhood asthma.