Asthma is the most common chronic illness in children and is a leading cause of childhood hospitalization and school absenteeism. Asthma presents with different phenotypes depending on age, gender, genetic background, environmental exposures and epigenetic factors. Forkhead box O3 (FOXO3) is a transcription factor involved in the pathogenesis of a number of inflammatory and respiratory diseases. The study aims to investigate the association between the SNP rs13217795 in FOXO3 gene and pediatric onset asthma in the Egyptian population. Ninety asthmatics and 160 healthy controls were subjected to genotyping of FOXO3 SNP (rs13217795) using the PCR-RFLP method. The proportion of homozygous (CC) and heterozygous (CT) genotypes was lower in the asthmatic group compared to the control group but statistically insignificant; P > 0.05. On the other hand the proportion of the mutant homozygous (TT) genotype in asthmatic group was higher; 30 (33.3%) than the control group; 28(17.5%), the difference was significant in Recessive model of disease penetrance with Odds ratio OR (95% CI) of 2.4(1 – 5.49) and P=0.039. This association was more pronounced in male gender; OR and 95% CI of 5.3 (1.4- 19.3) and P=0.01. In conclusions, Egyptian children carrying the mutant (TT) genotype were at higher risk to develop asthma with a higher risk in male gender.Copyright© by the Egyptian Association of Immunologists.