p53 as a tumor suppressor protein has been implicated in multiple aspects of biological processes, including apoptosis, cell cycle arrest, senescence, metabolism, differentiation and angiogenesis. Recently, several studies have shown that p53 can induce autophagy in both transcription-dependent and -independent manners. Nonetheless, p53 may also inhibit autophagy. In addition, p53 participates in homeostatic regulation of energy metabolism, oxidative stress and amino acid metabolism. Although the relationship between autophagy and p53 is quite complicated, and has not been well elucidated, p53 may underlie key aspects of metabolism and cancer biology. Thus, understanding the novel functions of p53 may allow us to develop new anticancer therapeutic approaches.