The invention provides a lipid-mixed poly (lactic-co-glycolic acid) (PLGA) nanoparticle having a high drug loading amount and an active targeting effect. The nanoparticle is of a core-shell structure, wherein the core is a poly (lactic-co-glycolic acid) (PLGA), and distearoyl-phosphatidylethanolamine-polyethylene glycol-folic acid and cholesterol-arginine-histidine methyl ester are embedded in the surface of the core. The nanoparticle disclosed by the invention can be used for remarkably improving the drug loading amount and the encapsulation efficiency of adriamycin, enhancing the cytotoxicity of the adriamycin to tumor cells and presenting a certain anti-multidrug resistance activity; the nanoparticles loaded with the adriamycin are mainly concentrated in tumor tissues after entering a body, so that the anti-tumor effect of the adriamycin is improved, and toxic and side effects are remarkably reduced; and a new strategy for the development of antitumor pharmaceutical preparations is provided.