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Honokiol (HK) shows potential application in cancer treatment, but its poor water solubility restricts clinical application greatly. In this paper, monomethoxy poly(ethylene glycol)–poly(lactic acid) (MPEG–PLA) was synthesized by ring-opening polymerization and processed into nanoparticle for honokiol delivery. Chemical structure of the synthesized polymer was confirmed by 1H NMR, and its molecular weight was determined by gel permeation chromatography (GPC). Honokiol loaded MPEG–PLA nanoparticles were prepared by solvent extract method. And particle size distribution, morphology, drug loading, drug release profile and anticancer activity in vitro were studied in detail. The described honokiol loaded MPEG–PLA nanoparticles in this paper might be a novel formulation for honokiol delivery.