Tumor-targeted nanoparticle delivery system has been known as a substitute and capable achievement in cancer treatment compared to conventional methods. In this study, we examined potential application of ɑ-tocotrienol-Precirol formulation to enhance efficiency of doxorubicin (DOX) in induction of apoptosis in HUH-7 hepatocarcinoma cells. ɑ-tocotrienol-loaded nanoparticles were characterized at the point of zeta potential, particle size, scanning electron microscope (SEM), and cell internalization. To evaluate antiproliferative effects of formulation, apoptosis, cell cycle procedure, flow cytometry, and MTT assays were employed. Optimum size of the ɑ-tocotrienol formulation revealed narrow size distribution with mean average of 78 ± 3 nm. IC50 values for ɑ-tocotrienol and ɑ-tocotrienol-nano structured lipid carriers after 24 h were 15 ± 0.6 and 10 ± 0.03 µM, respectively. After incubation of cells with ɑ-tocotrienol-loaded careers, the rate of cell proliferation decreased from 53 ± 6.1 to 34 ± 7.1% (P < 0.05). A significant improvement in the apoptosis percentage was revealed after treatment of the HUH-7 cell line with DOX and ɑ-tocotrienol careers (P < 0.05). Gene expression results demonstrated a marked decrease in survivin and increase in Bid and Bax levels. Our findings suggest that ɑ-tocotrienol-loaded nanoparticles elevate DOX efficacy in HUH-7 hepatocarcinoma cell.