OBJECTIVE： To synthesize Monomethoxy-polyethyleneglycolcyanoacrylate-co-poly-hexadecylcyanoacrylate （mPEG- PHDCA）， prepare adriamycin-loaded mPEG-PHDCA nanoparticle and study its in vitro drug release behavior. METHODS： Knoevenagel reaction and anionic polymerization were adopted to synthesize mPEG-PHDCA， and it was characterized with 1H-NMR. Weight-average molecular weight and polydispersity index （PDI） were determined by gel permeation chromatography （GPC）. Using adriamycin as model drug， complex emulsion-solvent evaporation method was used to prepare adriamycin-loaded mPEG-PHDCA nanoparticle. TEM was adopted to observe its micromorphology； particle size and Zeta potential were determined by particle size instrument. The content of adriamycin， drug-loading amount and encapsulated efficiency in nanoparticle were determined by HPLC. The characteristics of drug release in vitro were investigated by dialysis bag method. The drug release in vitro of it was compared with that of adriamycin. RESULTS： After characterized with 1H-NMR and GPC， mPEG-PHDCA was synthesized successfully； mass average molar mass was about 6 000， and PDI was 1.13. Prepared adriamycin-loaded mPEG-PHDCA nanoparticle was round ball-like granule and had smooth appearance， uniform size and good distribution without agglomeration. Particle size， Zeta-potential， drug-loading amount and entrapment efficiency were （94.61±3.91） nm， （－11.68±0.83） mV， （2.17±0.67）％， （79.54±4.66）％ （n＝3）. Accumulative release rate of adriamycin-loaded mPEG-PHDCA nanoparticle reached 85.38％ within 48 h. Drug release curve was Weibull equation distribution （R2＝0.979 4）. The adriamycin solution was released completely in vitro after 4 h. CONCLUSIONS： mPEG-PHDCA is synthesized with good drug loading efficiency， biocompatibility and sustained-release properties. It is expected to be a new nano drug delivery carrier.