A novel preparation method for core/shell nanoparticles with hydrophilic polymeric shell was designed and characterized. The core is composed of poly(lactide-co-glycolide) and polymeric shell is composed of pluronics (poly (ethylene oxide)-poly (propylene oxide)-poly(ethylene oxide) triblock copolymer, F-127) and hyaluronic acid (HA). The role of core is to provide the nucleus for the stable formation of hydrophilic polymeric shell by physical adsorption and that of polymeric shell is to provide the hydrophilic network for protein loading. Lysozyme, which was used as a model drug and protonated in the physiological pH, was successfully loaded into polymeric shell up to 7 wt% via ionic interaction between HA and lysozyme and the sustained release pattern was observed, which was due to the stable immobilization of lysozyme in the polymeric shell.