Abstract: A novel polymer material N-glycyrrhetinic acid(GA)-polyethylene glycol(PEG)-chitosan(NGPC)was used as a targeting carrier of Brucine, and then the Brucine-loaded NGPC-NPs(Brucine/NGPC-NPs)were prepared by ionic crosslinking method. The effect of the action of brucine, the brucine concentration, GA and endocytic inhibitors on the cell uptakes of Brucine solution and Brucine/NGPC-NPs were investigated in human HepG2 hepatocellular carcinoma cells. The confocal laser scanning microscopy was used to observe qualitatively the nanoparticles internalization. The results showed that the mean size of Brucine/NGPC-NPs were(197. 6±11. 2)nm; the drug encapsulation efficiency and loading content was(63. 48±4. 67)% and(5. 49±0. 38)%, respectively. The cellular uptake of Brucine solution and Brucine/NGPC-NPs were time-and concentration dependent. In particular, the Brucine/NGPC-NPs could be more efficiently taken up by cells than Brucine solution, with a significant active transport characteristics. Moreover, the presence of free glycyrrhetinic acid could decrease the cell uptake of Brucine/NGPC-NPs, indicating that the uptake of nanoparticles might mainly rely on clathrin-mediated endocytosis, and then internalized by cells. Hence, NGPC-NPs could be a targeting carrier to facilitate the delivery of encapsulated Brucine into the human hepatic cancer cells, achieving the goal of reducing poison and increasing effects.