To enhance the tumor-targeting and tumor cell-specific drug-release capacity of nano drug delivery systems, a magnetic resonance imaging-traceable, magnetic-targeted nanoplatform is developed, and the nanoplatform is prepared by capping mesoporous silica (MSN)-coated iron oxide nanoparticles (IONPs) with programmable DNA hairpin sensor "gates." In normal cells (HL-7702, human liver cells), the nanoplatform is able to entrap the loaded drugs, showing an "OFF" state; the nanoplatform is activated by endogenous miRNA-21 overexpressed in tumor cells (HepG2, human liver tumor cells), which serve as an exclusive key to unlock the nanoplatform through hybridization with programmable DNA hairpin, leading to a rapid drug release, showing an "ON" state. The nanoplatform exhibits high antitumor efficacy and low toxicity in in vitro and in vivo studies owing to its magnetic targeting and tumor cell-activated properties, paving the way for targeted and personalized tumor treatment and showing potential for clinical applications.