Tip60, a cellular protein with intrinsic histone acetyltransferase activity, plays an important role in DNA damage repair and apoptosis. Recent studies have suggested that Tip60 acts either as a transcriptional coactivator or corepressor. Daxx, a protein binding with various factors involved in cell death regulation, was found to interact with Tip60. The interaction between Tip60 and Daxx through the HAT domain was confirmed by coimmunoprecipitation. Luciferase reporter gene assay and chromatin immunoprecipitation assay reveal that Tip60 and Daxx repress the transcriptional activity of NF-κB. In this report, we suggest that Tip60 is a corepressor of the NF-κB-mediated transcriptinal activity in part through the recruitment of Daxx to promoters of NF-κB responsive genes.