Background: Bronchial asthma is a common disease with multiple determinants that include genetic variation. Signal transducer and activator of transcription 6 (STAT6) is a central molecule in the signal transduction pathway used by interleukin-4 (IL-4) in immunoglobulin E (IgE) isotype switching. Study Objective was to investigate whether single nucleotide polymorphism (SNP) in STAT6 is associated with atopic asthma susceptibility in Egyptian children and to correlate the effect of STAT6 gene polymorphism on IL-4 and total IgE levels. Methods and Findings: the study was conducted on 60 children with atopic asthma in addition, 30 healthy children as controls. The enzyme-linked immunosorbent assay technique (ELISA) was used to measure serum IL-4 and total IgE levels. Genotyping pattern for the STAT6 rs324011 polymorphism was done using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Discussion: Our data revealed that rs324011 TT genotype was significantly associated with increased susceptibility of developing bronchial asthma (OR=5.55, 95% CI=1.43-21.44) in comparison to rs324011 CC and CT genotypes. Meanwhile, in bronchial asthma group, serum IL-4 and total IgE levels were higher in patients with CT and TT genotypes compared to those with CC genotype. Conclusion: The T allele variant of STAT6 rs324011 polymorphism may be associated with increased susceptibility of the development of atopic bronchial asthma in Egyptian children; however, further studies are needed to verify these preliminary results.