The signal transducer and activator of transcription 6 (STAT6) transduces signals in response to IL-4 and IL-13 cytokine stimulations, resulting in many cell-specific responses. Some common STAT6 SNPs were associated with asthma predisposition and/or IgE levels, although discrepancies have also been reported.To determine whether STAT6 rs324011 and rs324015 polymorphisms are associated with atopic asthma in Saudi Arabian patients.A total of 536 Saudi individuals aged 11-70years old (230 atopic asthmatics, 306 healthy subjects) were recruited. DNA was purified from peripheral blood and genotyping for rs324011 and rs324015 polymorphisms was performed by PCR amplification, followed by cycle sequencing of the purified PCR fragments using BigDye chain terminator and capillary electrophoresis.By the contrast of alleles tests, no significant differences between asthma and healthy groups were detected for both variants (rs324011: X(2)=0.25, Pearson's P-value=0.617; rs324015: X(2)=0.068, Pearson's P=0.814).When testing for genotypes, rs324011 homozygous T/T genotype was significantly associated with asthma, when the Recessive model is considered (T/T vs. C/C+C/T) (adjusted, OR=2.49, 95% CI=1.18-5.25, Pearson's P=0.014(∗), Yates' P=0.022(∗)). In contrast, rs324015 variant was not significantly associated with asthma.Rs324011 homozygous T/T genotype was significantly associated with asthma risk whereas rs324015 genotypes were not in the Saudi population.