IkappaBzeta belongs to the nuclear members of the IkappaB protein family. Its function in regulating the activity of the transcription factor NFkappaB is poorly understood. Here, we demonstrate that human IkappaBzeta is posttranscriptionally regulated by microRNA (miR)-124a. In HepG2 cells miR-124a was not endogenously expressed, but upon enforced expression dramatically inhibited the interleukin-1beta-induced protein expression of IkappaBzeta. The predicted binding site for miR-124a in the 3'UTR of the IkappaBzeta mRNA revealed an imperfect match resulting in miR-124a-mediated suppression of IkappaBzeta expression through translational repression. Reporter gene analyses revealed that miR-124a targets IkappaBzeta mRNA through base pairing to the partially complementary sequence in the 3'UTR that was predicted as a binding site by in silico analysis. Furthermore, we demonstrate that the 7mer seed match is sufficient for recognition of the IkappaBzeta mRNA. Together, our data identify IkappaBzeta as a target of miR-124a that might be involved in the fine-tuning of NF-kappaB-mediated gene expression.