Antisense compounds, compositions and methods are provided for modulating the expression of IL-1 receptor-associated kinase-4. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding IL-1 receptor-associated kinase-4. Methods of using these compounds for modulation of IL-1 receptor-associated kinase-4 expression and for treatment of diseases associated with expression of IL-1 receptor-associated kinase-4 are provided.