We have successfully constructed a smart therapeutic platform with potential controllable drug release and magnetic hyperthermia through the conjugation of carboxyl-modified DNA₂₀ onto aminated magnetic mesoporous silica nanoparticles (MMSNs). Drug release behavior, magnetic heating capacity, in vitro cytotoxicity, and cell uptake of the magnetic nanosystem were evaluated. The results showed that the magnetic nanosystem could control the doxorubicin (DOX) release behavior with a reversible temperature response. Also, the MMSN-NH₂ nanoparticles could efficiently generate heat upon exposure to an alternating magnetic field due to their superparamagnetic behavior. Furthermore, the MMSN-NH₂ nanoparticles could be effectively taken up by HeLa cells, and negligible cytotoxicity has been observed for the MMSN-NH₂ nanoparticles. Therefore, this magnetic nanosystem has potential for cancer therapy with controlled drug release and magnetic hyperthermia.