Tea (Camellia sinensis L.) is the most popular, flavored, functional, and therapeutic non-alcoholic drink consumed by two-thirds of the world's population. Black tea leaves are reported to contain thousands of bioactive constituents such as polyphenols, amino acids, volatile compounds, and alkaloids that exhibit a range of promising pharmacological properties. Due to strong antioxidant property, black tea inhibits the development of various cancers by regulating oxidative damage of biomolecules, endogenous antioxidants, and pathways of mutagen and transcription of antioxidant gene pool. Regular drinking of phytochemicals-rich black tea is linked to regulate several molecular targets, including COX-2, 5-LOX, AP-1, JNK, STAT, EGFR, AKT, Bcl2, NF-κB, Bcl-xL, caspases, p53, FOXO1, TNFα, PARP, and MAPK, which may be the basis of how dose of black tea prevents and cures cancer. In vitro and preclinical studies support the anti-cancer activity of black tea; however, its effect in human trails is uncertain, although more clinical experiments are needed at molecular levels to understand its anti-cancer property. This review discusses the current knowledge on phytochemistry, chemopreventive activity, and clinical applications of black tea to reveal its anti-cancer effect.