Background:Worldwide, asthma is a major public health issue due to its high prevalence and debilitating effects. Asthma prevalence in children has steadily risen over the last 20 years. Asthma affects 300 million people worldwide and is expected to rise from 45% to 59% by 2025, according to estimates. Bronchial asthma affects 5-10% of children and teenagers. Objective:To Explore the correlation of NQO1 gene polymorphism and risk factors of childhood asthmaPatients and methods:Thisis a case control study. Theparticipants were divided into two main groups, 29 nonasthmatics as a control group, and 87 asthmatic children as cases.The cases were further subdivided into 3 subgroups according to their asthma control level. All children were assessed for the pulmonary functions. Genotyping of Nicotinamide adenine dinucleotide phosphate Quinone Oxidoreductase 1 gene polymorphism was assessed by restriction fragment length polymerase chain reaction (RFLP_PCR). Results:Patients with uncontrolled, partially controlled, and well-controlled asthma were more likely to have family members who had asthma (96.6%, 86.2%, and 72.4%, respectively).FEV1 percent and FVC differed significantly between the four groups. There was statistically significant difference between the four studied groups as regard gene polymorphism, 75.9% of control group had CC genotype and 58.6% of uncontrolled asthmatic patients had CT genotype. The asthma group in the study had less CC genotype and C allele (42.5% & 67.8%) versus the control group (75.9% & 87.9%) Conclusion:The study has revealed a significant correlation between family history of asthma and the childhood asthma. The polymorphisms of NQO1 are correlated with the risk of childhood asthma, and it increases due to the dominant homozygous mutations of NQO1.