PURPOSE: The aim of this study was to evaluate radiofrequency-induced dextran-coated lanthanum strontium manganese oxide nanoparticles-mediated hyperthermia to be used for tumor regression in mice. MATERIALS AND METHODS: Nanoparticles were injected intra-tumorally in melanoma-bearing C57BL/6J mice and were subjected to radiofrequency treatment. RESULTS: Hyperthermia treatment significantly inhibited tumor growth (84%), increased survival (50%), and reduced tumor proliferation in mice. Histopathological examination demonstrated immense cell death in treated tumors. DNA fragmentation, increased terminal deoxynucleotidyl transferase-dUTP nick end labeling signal, and elevated levels of caspase-3 and caspase-6 suggested apoptotic cell death. Enhanced catalase activity suggested reactive oxygen species-mediated cell death. Enhanced expression of heat shock proteins 70 and 90 in treated tumors suggested the possible development of "antitumor immunity". CONCLUSION: The dextran-coated lanthanum strontium manganese oxide-mediated hyperthermia can be used for the treatment of cancer.