Flash nanoprecipitation (FNP) is a recent developed method featuring fast processing and simple equipment for preparing drug-carrier NPs. Herein, we prepared stable sorafenib-loaded NPs with biocompatible amphiphilic poly(ethylene glycol)-block-poly(lactide acid) (PEG-b-PLA) as stabilizing polymer based on FNP. The formed NPs show well-controlled size and high drug loading content compared with nanoparticles from traditional antisolvent precipitation. Moreover, drug/polymer mass ratio (D/P) and stream velocity presented as Reynolds number (Re) show strong effects on particles size and internal morphology. Low D/P ratio and Re number provide core-shell nano- particles with drug nuclei distributed in PLA matrix, which could release the sorafenib completely but keep the polymer aggregates after the drug release. While high D/P ratio and Re number lead to grained nanoparticles with bigger size and low packing density due to the coprecipitation of the PEG blocks in the structure. The drug release of these particles is fast and typically accompanied by the dissociation of the nanoparticles. Our study demonstrates that the particle internal morphology and solute packing density are crucial factors to manipulate the drug release of the FNP nanoparticles, and the developed strategy could be widely adopted to assess drug release of FNP nanoparticles for further therapeutic applications.