We report on a novel drug carrier which is based on the combination of magnetic and upconversion (UC) emission of Fe3O4@SiO2/NaYF4:Yb, Er (MSU) hybrids modified with MnO2 nanosheets (MSU/MnO2). The MSU hybrids were fabricated by covalently linking amino-modified Fe3O4@SiO2 particles with carboxyl-functionalized NaYF4:Yb, Er particles. The Fe3O4 core and the NaYF4:Yb, Er shell functioned successfully for magnetic targeting and fluorescence imaging, respectively. MnO2 nanosheets served as drug carriers and UC luminescence quenchers. The drug can be released by introducing glutathione (GSH) which reduces MnO2 to Mn(2+), and at the same time, UC luminescence can be turned on. These results clearly show that these MSU/MnO2 nanocomposites are promising platforms which can be applied to construct a smart drug delivery system with magnetic targeting and GSH-stimulation, as well as tracking by UC luminescence.