The TP53 (p53) protein is a well-known tumor suppressor that plays a crucial role in maintaining genome stability under various cellular stresses. Loss of TP53 causes lymphomagenesis in mouse models and/or promotes tumor progression. However, the prognostic significance of TP53 has been inconsistent in human cancers including malignant lymphoma. In our recent review of TP53 dysfunction in lymphoid malignancies, we discussed the fact that the TP53 function in autophagy may be one of the important mechanisms responsible for the inconsistency of TP53 prognostic value, in that autophagy can promote survival of lymphoma cells by recycling toxic intracellular materials and inhibiting apoptosis. Here we discuss the biological mechanisms of TP53 functional switches from apoptosis to autophagy, and provide a brief summary of how TP53 regulates autophagy through its transcriptional activity on 14 genes of the TP53 pathway.