Background:  Asthma is a complex disease resulting from interactions between multiple genes and environmental factors. Study of gene–gene interactions could provide insight into the pathophysiology of asthma.Methods:  We investigated the interactions among 18 single‐nucleotide polymorphisms in eight candidate genes for plasma total immunoglobulin E (IgE) concentration and peripheral blood (PB) eosinophil count in 298 Chinese asthmatic children and 175 controls. Generalized multifactor dimensionality reduction and generalized linear model were used to analyze gene–gene interactions for the quantitative traits.Results:  A significant interaction was found between R130Q in IL13 and I50V in IL4RA for plasma total IgE concentration, with a cross‐validation (CV) consistency of nine of 10 and a prediction error of 41.1% (P = 0.013). Plasma total IgE concentration was significantly higher in the high‐risk than the low‐risk groups (P < 0.0001). For PB eosinophil count, significant interaction was found between C‐431T in TARC and RsaI_in2 in FCERIB, with a CV consistency of nine of 10 and a prediction error of 40.2% (P = 0.009). PB eosinophil count was significantly higher in the high‐risk group than the low‐risk groups (P < 0.0001). Generalized linear model also revealed significant gene–gene interaction for the above two endophenotypes with P = 0.013 for plasma total IgE concentration and P = 0.029 for PB eosinophil count respectively.Conclusions:  Our data suggest significant interactions between IL13 and IL4RA for plasma total IgE concentration, and this is the first report to show significant interaction between TARC and FCERIB for PB eosinophil count in Chinese asthmatic children.