Lupeol nanoparticles (lupeol-NPs) utilizing a PEG-PLGA diblock copolymer vector were developed, and it indicated that Lupeol-NPs counteracted the radioresistance of hepatocellular carcinoma by suppressing cellular proliferation and cell-cycle progression while enhancing cellular apoptosis through the inhibition of Raf/MAPK and PI3K/AKT signaling pathways in radioresistant Huh-7R cells. The gene discussed is AKT1; the disease is hepatocellular carcinoma.