Chemotherapeutic drugs induce NF-κB/p53 crosstalk in cell lines and primary cells. HDACi antagonize p53-dependent anti-apoptotic NF-κB-dependent gene expression. HDACi against class I HDACs reduce p53 levels in various tumor cells. Class I HDACi are necessary for the crosstalk between mutant p53 and NF-κB. Highly specific HDACi are tools to disclose biological functions of HDACs.