Polymer-modified nanoparticles, which can load anticancer drugs such as doxorubicin (DOX), showing the release in response to a specific trigger, have been paid much attention in cancer therapy. In our study, a pH-sensitive drug-delivery system consisting of Fe3O4@mSiO2 core−shell nanocomposite (about 65 nm) and a β-thiopropionatepoly( ethylene glycol) “gatekeeper” (P2) has been successfully synthesized as a drug carrier (Fe3O4@mSiO2@P2). Because of the hydrolysis of the β- thiopropionate linker under mildly acidic conditions, Fe3O4@mSiO2@P2 shows a pH-sensitive release performance based on the slight difference between a tumor (weakly acid) and normal tissue (weakly alkaline). And before reaching the tumor site, the drug-delivery system shows good drug retention. Notably, the nanocomposites are quickly taken up by HeLa cells due to their small particle size and the poly(ethylene glycol) modification, which is significant for increasing the drug efficiency as well as the cancer therapy of the drug vehicles. The excellent biocompatibility and selective release performance of the nanocomposites combined with the magnetic targeted ability are expected to be promising in the potential application of cancer treatment.