OBJECTIVE： To study the in vitro uptake of Resibufogenin （RBG） lactic acid glycolic acid copolymer-water soluble vitamin E （PLGA-TPGS） in human liver cancer HepG2 cells， mouse ascites-type lymphatic metastasis of tumor HCa-F cells， and the toxicity on HepG2 cells. METHODS： RCPTN loading RBG and coumarin-6 （C6） were prepared. Fluorescent inverted microscope was used to observe the in vitro uptake by RCPTN HepG2， HCa-F cells. It was divided into negative control group， blank PLGA-TPGS nanoparticles （EPTN） group， 5-fluorouracil solution （FS） group， RBG solution （RS） group， RBG/PLGA nanoparticles （RPN） group and RPTN group. WST-1 was conducted to investigate the optical density at 450 nm wavelength of HepG2 cells after 24， 48， 72 h incubated by FS， RS， RPN and RPTN with different final concentrations （1.25， 2.5， 5， 10， 20 μg/mL）； the cell viability （CV） and half inhibitory concentration （IC50） were calculated. RESULTS： RCPTN distributed around the nucleus of HepG2， HCa-F cells. CV was decreased by RBG concentration increased in RPN group and RPTN group， and decreased by time prolonged； compared with FS group， CV in RPTN group was decreased （P＜0.05 or P＜0.01）. IC50 of HepG2 cells incubated by FS， RS， RPN and RPTN was decreased by time prolonged， ordered by RS＞FS＞RPN＞RPTN； IC50 incubated by RPN and RPTN for 48， 72 h was obviously less than that of FS and RS （P＜0.05 or P＜0.01）. CONCLUSIONS： RPTN can deliver RBG into HepG2， HCa-F cells， showing inhibition effect on HepG2 cells which is stronger than RPN， RS and FS.