The prophylactic and therapeutic properties of tea have been attributed to green tea catechins and black tea theaflavins besides several other polyphenolic compounds. Tea polyphenols possess potent antioxidant and antiinflammatory properties and modulate several signaling pathways. These biochemical facets of tea polyphenols are responsible for its anticancer properties. Several lethal cancers, such as liver cancer, develop within a background of oxidative stress and inflammation. Liver cancer, also known as hepatocellular carcinoma (HCC), has been shown to occur throughout the world including Asia, Africa, Western Europe, and the United States. Phytochemicals, such as tea polyphenols, provide an effective and promising alternative for the chemoprevention and treatment of HCC. In this article, we systematically review, for the first time, the effects of tea polyphenols in the preclinical in vitro and in vivo HCC models. The review also examines, in critical detail, the biochemical mechanisms involved in the chemopreventive and antineoplastic effects of tea polyphenols in hepatic cancer. Finally, we highlight the role of synergy, bioavailability and pharmacokinetics of tea polyphenols, current status of clinical trials, discuss future directions, and comment on the future challenges involved in the effective use of tea polyphenols for the prevention and management of liver cancer.