The natural dietary product tea (Camellia sinensis) and its bioactive polyphenols such as epigallocatechin gallate (EGCG) and theaflavin (TF) demonstrated potential anticancer effects in different preclinical and clinical studies. The aim of the present review was to understand the molecular mechanisms of the tea and tea polyphenol-mediated cancer prevention and therapy. In the setting of in vivo cancer prevention studies, administration of the tea and tea polyphenols at preinitiation stages only showed partial prevention, whereas continuous administration showed potential effect in restriction of carcinogenesis in the body's multiple organs at early premalignant stages throughout the experiment. Similar to different in vitro cancer cell models, treatment after initiation stages showed potential therapeutic efficacy in vivo. But, the mechanisms of prevention and therapy were found to be similar regardless of tea and its polyphenols. They mainly serve as antioxidants and induce the detoxification system, thereby inhibiting carcinogen metabolism and cancer initiation. Additionally, they could inhibit self-renewal, proliferation, and survival of the tumor-initiating population in restriction of the carcinogenesis progression from cancer initiation and promotion. This might be a result of the modulation of membrane organization, interaction with DNA/RNA/proteins and epigenetic modifications, as well as regulation of cellular replicative potential by the tea polyphenols.