Recent studies from our groups and others’ have shed new lights on various aspects of p53 regulation by HIPK2 and have served to both increase the complexity of the p53 regulatory pathways, including p53 inhibitors (i.e., MDM2) and p53-family members (i.e., ΔNp63α) but also to underline a role for HIPK2 as tumor suppressor itself for anticancer therapy, that we will discuss here. Here, HIPK2 is linked to neoplasm.