Vitamin E is the generic name for tocopherol (Toc) and tocotrienol (T3), which have saturated and unsaturated side chains, respectively. Such differences allow T3 to be different from Toc in terms of their functions. T3 has been known to attenuate cholesterol (Cho) level by inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoAR). Recent reports also showed the efficacy of T3 in improving triglyceride (TG) profiles in both in vivo and in vitro studies. However the mechanism involved in this biological activity is still unclear and needs to be further investigated. In the present study, we elucidated the effect of γ-T3 on lipid levels and lipogenic gene expressions in mouse hepatocellular carcinoma Hepa 1-6. γ-T3 showed attenuation of TG through effect on fatty acid synthase, sterol regulatory element-binding transcription factor 1, stearoyl CoA desaturase 1, and carnitine palmitoyl transferase 1A gene expression in Hepa 1-6. In contrast, the Cho level remained unchanged. These results expanded our previous finding of lipid-lowering effects of T3, especially for TG. Therefore, T3 is a potential lipid-lowering compound candidate with realistic prospects for its use as a therapy for lipid-related diseases in humans.