OBJECTIVE To prepare Curcumin-loaded methoxy polyethylene glycol-polylactic acid (mPEG-PLA) nanoparticles (CUR-mPEG-PLA-NPs), characterize their physicochemical properties, study the in vitro release behavior and antitumor activity on SMMC-7721 ceils.METHODS The CUR-mPEG-PLA-NPs were prepared by emulsification-solvent evaporation method and the formulation was optimized through orthogonal test.The transmission electron microscope, Zetasizer instrument, ultracentrifugation were utilized to characterize the properties of the nanoparticles.Dynamic dialysis method was used to study the in vitro release behavior of the nanoparticles.The antitumor activity on SMCC-7721 cells was determined by MTT method.RESULTS The optimized nanoparticles were found to be of nanometric size (129.24±1.45) nm, with low PI (0.208±0.007) and high encapsulation efficiency (82.15±1.07) %, drug loading (4.03±0.11) %.The in vitro release behavior showed a significant sustained release profile in PBS buffer composed of 1% Polysorbate 80 at pH 5.8.Compared with free CUR, CUR-mPEG-PLA-NPs showed stronger cytotoxicity and compatibility with hepatoma cells SMMC-7721.CONCLUSION The prepared nanoparticles are available with small particle size, high encapsulation efficiency, and a certain sustained release characteristics, which could lay the foundation for the research on novel CUR preparations.