The tumor suppressor gene p53 is a key regulator of cell growth and apoptosis, and its loss of function due to mutations or other mechanisms is frequently observed in cancer. Recent research has elucidated the complex role of p53 in cancer development and progression, providing insights into potential therapeutic strategies. In this commentary, we review some of the previous articles on p53, focusing on the current understanding of its function in cancer and the therapeutic approaches targeting the p53 pathway. This article discusses the diverse mechanisms underlying p53 inactivation in cancer, including somatic mutations, epigenetic alterations, and deregulated expression of p53 regulators. It also highlights recent efforts to reactivate mutant p53, restore wild-type p53 function, or target downstream effectors of the p53 pathway as potential strategies for cancer therapy. Overall, this commentary provides an overview of the current knowledge on the tumor suppressor gene p53 and its potential as a target for cancer treatment.