The invention belongs to the field of medicinal preparations, and relates to a targeted nanometer delivery release system aiming at a multidrug resistant tumor and a preparation method of the targeted nanometer delivery release system. According to the system and the preparation method, the photosensitizer, namely, pyrophaeophorbide-a (PPA) is bonded to two ends of the copolymer, namely, hydroxylated-polylactic acid-polyglycolic acid (HO-PLA-PEG-PLA-OH) through a chemical bonding method, thus the product, namely, the photosensitizer-embedded polylactic acid-polyglycolic acid polymer (PPA-PLA-PEG-PLA-PPA) is obtained, then the chemotherapy medicine, namely, paclitaxel is encapsulated physically by adopting an emulsified solvent evaporation method, thus the binary-drug-loading nanometer delivery release system (PPA NP-PTX) is prepared, then F3 peptide with the specific targeting function and the cell penetrating function is modified on the surface of the system, and thus the photodynamic therapy and chemotherapy combined drug delivery nanometer delivery release system with the binary targeting property is prepared. The experiment proves that the delivery system has the strong lethal effect for drug resistant tumor cells, has the obvious in-vivo tumor targeting effect, and has the obvious treatment effect for the mice bearing the multidrug resistant tumor, and thus the combined drug delivery nanometer system has the clinical application prospect.