The article reviews the role of TP53 mutations in immune evasion in cancer and explores therapeutic strategies to enhance anti-tumor immunity. TP53 mutations are prevalent in various cancers and confer resistance to apoptosis and cell cycle arrest, contributing to multidrug resistance. Recent studies have highlighted the immunomodulatory functions of p53, which are underappreciated compared to its well-known roles in cell cycle regulation and genomic stability. The review summarizes mechanisms by which p53-mutant tumors evade immune surveillance from T cells, natural killer (NK) cells, and macrophages, and how these tumors reshape the tumor microenvironment (TME) to foster immunosuppression. Clinical observations indicate that p53 loss or mutations are associated with poor responses to immunotherapy. The article discusses therapeutic strategies, including the use of MDM2 inhibitors, STING agonists, p53-restoring agents, and immune-based therapies, to enhance immune response against p53-mutant tumors. These strategies aim to overcome immune evasion and improve clinical outcomes in patients with p53-mutant cancers.The article reviews the role of TP53 mutations in immune evasion in cancer and explores therapeutic strategies to enhance anti-tumor immunity. TP53 mutations are prevalent in various cancers and confer resistance to apoptosis and cell cycle arrest, contributing to multidrug resistance. Recent studies have highlighted the immunomodulatory functions of p53, which are underappreciated compared to its well-known roles in cell cycle regulation and genomic stability. The review summarizes mechanisms by which p53-mutant tumors evade immune surveillance from T cells, natural killer (NK) cells, and macrophages, and how these tumors reshape the tumor microenvironment (TME) to foster immunosuppression. Clinical observations indicate that p53 loss or mutations are associated with poor responses to immunotherapy. The article discusses therapeutic strategies, including the use of MDM2 inhibitors, STING agonists, p53-restoring agents, and immune-based therapies, to enhance immune response against p53-mutant tumors. These strategies aim to overcome immune evasion and improve clinical outcomes in patients with p53-mutant cancers.