The p21 protein, encoded by CDKN1A, plays a vital role in the induction of senescence, and its transcriptional control by p53 tumour supressor is well-established. However, p21 can also be regulated in a p53-independent manner, by mechanisms that remain poorly understood. Therefore, we here used a chromatin-directed proteomic approach and identified ZNF84 as a novel regulator of p21 in various p53-deficient cell lines.