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To overcome the shortcoming of drug-loaded nanoparticles, such as high initial burst release and wide size distribution, a novel manufacturing technique for core-shell structure nanoparticle was developed by combining microfluidic chip and electrohydrodynamic atomization. In this study, the mixture solution of the surfactant 1, 2- dipalmitoyl-sn-glycero-3-phosphoglycerol and the polymeric coating material polylactic-glycolic-acid was introduced into the outer microchannel of the microfluidic chip as the particle's shell. And the encapsulated drug paclitaxel was pumped into the inner microchannel as the core. Then, the particles with a nanoscale-size core-shell structure were generated by applying an electric field on the laminar flow which was formed in the microfluidic chip. Operation parameters, including working voltage, carrier material and surfactant concentration as well as liquid flow rates were optimized for nanoparticles generation. The properties of drug-loaded nanoparticles in terms of their particle size, zeta potential and encapsulation efficiency were investigated. Under the optimal experimental conditions, the particle size was approximately 145 nm and encapsulation efficiency reached 92%. Moreover, the drug release of these nanoparticles could be prolonged over a significant period for more than ten days. It can be expected that this innovative approach could provide a useful platform for drug-loaded core-shell nanoparticles developing.