The anticancer effects of polyphenols are ascribed to several signaling pathways including the tumor suppressor gene tumor protein 53 (p53). Expression of endogenous p53 is silent in various types of cancers. A number of polyphenols from a wide variety of dietary sources could upregulate p53 expression in several cancer cell lines through distinct mechanisms of action. The aim of this review is to focus the significance of p53 signaling pathways and to provide molecular intuitions of dietary polyphenols in chemoprevention by monitoring p53 expression that have a prominent role in tumor suppression.