The therapeutic efficiency of active targeting nanoparticulate drug delivery systems (nano-DDS) is highly compromised by the plasma proteins adsorption on nanoparticles (NPs) surface, which significantly hinders cell membrane receptors to recognize the designed ligands, and provokes the off-target toxicity and rapid clearance of NPs . Herein, we report a novel dihydroartemisinin (DHA)-decorating nano-DDS that specifically recruits endogenous apolipoprotein E (apoE) on the NPs surface. The apoE-anchored corona is able to prolong PLGA-PEG2000-DHA (PPD) NPs circulation capability in blood, facilitate NPs accumulating in tumor cells by the passive enhanced permeability and retention (EPR) effect and low-density lipoprotein receptor (LDLr)-mediated target transport, and ultimately improve the antitumor activity. Our findings demonstrate that the strategy of regulated apoE-enriched corona ensures NPs an efficient LDLr-mediated tumor-homing chemotherapy.