Despite the significant advancements in the diagnosis and treatment of cancer, it still remains one of the most fatal diseases in the world due to the lack of sensitive diagnosis methods and effective drugs. Therefore, discovering novel therapies that are safe, efficacious and affordable are required for the better management of this disease. Tocotrienols, analogues of vitamin E have gained increased attention due to their safety and efficacy. Extensive research over the past several years has strongly indicated that tocotrienols can efficiently prevent/inhibit the growth of different cancers such as cancers of blood, brain, breast, cervical, colon, liver, lung, pancreas, prostate, skin, stomach etc. This is mainly accredited to their ability to modulate various molecular targets involved in cancer cell proliferation, survival, invasion, angiogenesis, and metastasis such as NF-κB, STAT3, Akt/mTOR, etc. In addition, increasing lines of evidence has shown that tocotrienols can sensitize cancer cells to chemotherapeutic agents such as celecoxib, doxorubicin, erlotinib, gefitinib, gemcitabine, paclitaxel, statin etc. Moreover, several clinical trials have confirmed the safety and tolerability of tocotrienols in humans. This review summarizes the potential of tocotrienols for the prevention and treatment of different cancers based on the available in vitro, in vivo and clinical studies.