Magnetic nanoparticles (MNPs) have been widely investigated as a hyperthermic agent for cancer treatment. In this study, thermally responsive Chitosan-coated MnFe ₂ O ₄ (Chitosan-MnFe ₂ O ₄ ) nanoparticles were developed to conduct localized magnetic hyperthermia for cancer treatment. Hydrophobic MnFe ₂ O ₄ nanoparticles were synthesized via thermal decomposition and modified with 2,3-dimercaptosuccinic acid (DMSA) for further conjugation of chitosan. Chitosan-MnFe ₂ O ₄ nanoparticles exhibited high magnetization and excellent biocompatibility along with low cell cytotoxicity. During magnetic hyperthermia treatment (MHT) with Chitosan-MnFe ₂ O ₄ on MDA-MB 231 cancer cells, the targeted therapeutic temperature was achieved by directly controlling the strength of the external AC magnetic fields. In vitro Chitosan-MnFe ₂ O ₄ -assisted MHT at 42 °C led to drastic and irreversible changes in cell morphology and eventual cellular death in association with the induction of apoptosis through heat dissipation from the excited magnetic nanoparticles. Therefore, the Chitosan-MnFe ₂ O ₄ nanoparticles with high biocompatibility and thermal capability can be an effective nano-mediated agent for MHT on cancer.