A novel starch-based stimuli-responsive magnetite nanohydrogel (MNHG), namely FeO-g-[poly(N-isopropylacrylamide-co-maleic anhydride)]@strach; FeO-g-(PNIPAAm-co-PMA)@starch, was successfully developed for targeted delivery of doxorubicin (DOX) as an anticancer drug. First, magnetite nanoparticles (MNPs) was modified using chloroacetyl chloride moiety followed by grafting of NIPAAm and MA monomers through ATRP technique. The resultant FeO-g-(PNIPAAm-co-PMA) nanocomposite was crosslinked through the reaction between the anhydride group of MA and hydroxyl groups of starch to afford a FeO-g-(PNIPAAm-co-PMA)@starch MNHG. The chemical structure of the synthesized materials were confirmed using Fourier transform infrared (FTIR) spectroscopy. Furthermore, morphology, size, thermal property, and magnetic properties of the synthesized MNHG were studied. This MNHG was loaded with DOX, and drug loading and encapsulation efficiencies as well as pH- and temperature-responsive drug release behavior of the fabricated MNHG were also evaluated. As results, we envision that the developed MNHG has potential as de novo drug delivery system (DDS) due to its smart physicochemical features.