Tea is the most popular beverages all over the world. Polyphenols are found ubiquitously in tea leaves and their regular consumption has been associated with a reduced risk of a number of chronic diseases including cancer, cardiovascular and neurodegenerative diseases. Epigallocatechin-3-gallate (EGCG) is the most abundant polyphenol in tea leaves and received great attention due to their protective role in the prevention of the diseases. Rather than eliciting direct antioxidant effects, the mechanisms by which tea polyphenol express these beneficial properties appear to involve their interaction with cellular signaling pathways and related machinery that mediate cell function under both normal and pathological conditions. The central focus of this review is to provide an overview of the role that the major tea polyphenol, EGCG plays in preventing cancer, cardiovascular and neurodegenerative diseases. This review present epidemiological data, human intervention study findings, as well as animal and in vitro studies in support of these actions and delineates the molecular mechanism associated with the action of EGCG in ameliorating of such diseases.