In this paper, in order to take advantage of the combination between magnetic nano-Fe3O4 and surface modifier, a pH-sensitive drug delivery system that could effectively deliver doxorubicin (DOX) to tumor tissue was constructed. The novel drug delivery system named Fe3O4-TIPTS-g-(PEI-co-PEG) was prepared through three steps. The first step, a surface modifier with the thiol group, thiohydrazide-iminopropyltriethoxysilane surface modifier (named TIPTS), was synthesized for the first time. The second step, Fe3O4-TIPTS was synthesized by treating nano-Fe3O4 with TIPTS. The last step, Fe3O4-TIPTS-g-(PEI-co-PEG) was synthesized in the presence of the Fe3O4-TIPTS, polyethyleneimine (PEI), and polyethylene glycol (PEG) by mercapto-initiated radical polymerization. Among them, magnetic nanoparticles (MNPs) were used as magnetically responsive carriers, PEG was the surface-modifying compound, and PEI was the drug loading site which primary amine reacts with doxorubicin (DOX). Targeted nanoparticles were considerably stabilize in various physiological solutions and exhibited pH-sensitive performance in drug release. Thence, Fe3O4-TIPTS-g-(PEI-co-PEG) is a promising nanocarrier for targeting tumor therapy.