OBJECTIVE： To prepare Sinomenine （SIN）-loaded polylactic-co-glycolic acid-D-α-tocopheryl polyethylene glycol 1000 succinate （PLGA-TPGS） nanoparticles （SPTN）， and to study its uptake by cells and inhibitory effect on human liver cancer HepG2 cells. METHODS： Emulsification-solvent evaporation method was used to prepare SPTN with coumarin-6 （C6） as fluorescent marker （SCPTN） and sinomenine PLGA nanoparticles （SPN） with C6 as fluorescent marker （SCPN）. The particle size， Zeta-potential and drug-loading amount were detected， and flow cytometry was used to study the uptake of SCPTN and SCPN by HepG2 cells after adding different inhibitors （sodium azide， sucrose， cytochalasin B， genistein， methyl-β-cyclodextrin） and blank control. Using 5-fluorouracil solution （FS） as positive control， WST-1 was used to detect inhibitory rate （IR） of HepG2 cells 24， 48 and 72 h after cultured with 10， 20， 40， 80， 160 μg/ml SPTN， SPN and sinomenine solutions （SS）. RESULTS： Mean particle size of SCPTN and SCPN were （192.1±2.4） and （389.3±2.2） nm， Zeta potential （－21.5±2.6） and （－13.7±2.3） mV and drug-loading amount of sinomenine（9.3±1.7）％ and （6.1±1.8）％ （n＝6）. Compared with blank control， relative uptake rate of SCPTN and SCPN by HepG2 cells decreased after treated with sodium azide and sucrose （P＜0.01）； relative uptake rate of SCPTN by HepG2 cells decreased after treated with genistein （P＜0.05）； no other obvious change was found. Compared with SS， IR of HepG2 cells increased in concentration-dependent manner after treated with SPTN and SPN， while IC50 decreased （P＜0.05 or P＜0.01）； compared with FS， IR of HepG2 cells increased only after treated with 80 μg/ml SPTN for 72 h and 160 μg/ml SPTN for 48 and 72 h （P＜0.05 or P＜0.01）， and IC50 of HepG2 cells decreased after treated for 72 h （P＜0.05）. CONCLUSIONS： SPTN has been prepared successfully， and cellular uptake mechanism of it by HepG2 cells might be clathrin-mediated endocytosis. SPTN can inhibit the growth of HepG2 cells.