Despite its potent in vitro anti-cancer activity, the vitamin E extract tocotrienol has its therapeutic potential hampered by its poor bioavailability and by its inability to reach tumors in a specific way after intravenous administration. One possibility to overcome this issue would be to entrap tocotrienol within vesicles bearing transferrin, whose receptors are present in abundance on many cancer cell types. In this study, we demonstrated that the systemic administration of tocotrienol entrapped within transferrin-bearing vesicles led to tumor suppression of 20% of A431 epidermoid carcinoma tumors and 50% of B16-F10 melanoma tumors at the end of the treatment. The survival of animals treated with these vesicles was improved by more than 20 days in comparison with the controls, for the two cancer models tested. Animals did not show any secondary effects following administration of the treatment. The entrapment of tocotrienol within transferrin-bearing vesicles is therefore a promising therapeutic strategy, which could result in tumor suppression after systemic administration of this delivery system.