Cell entry into senescence is typically irreversible and is associated with heterochromatization of the genome, which is marked by the establishment of senescence-associated heterochromatin foci (SAHF). However, in contrast to many genes that are silenced on senescence entry (including pro-proliferative genes), the expression of factors such as cytokines and chemokines is induced in senescent cells and can promote oncogenic transformation of neighbouring cells through the senescence-associated secretory phenotype (SASP). Aird et al. now show that the chromatin-binding protein high mobility group box 2 (HMGB2) is an important regulator of the SASP, and that by binding to SASP gene loci it prevents their incorporation into SAHF and silencing. Thus, removal of HMGB2 could potentially be used to reduce the SASP and to restrain cancer-promoting effects associated with senescence.