Implantable thermo-responsive drug-loaded magnetic nanofibers (NFs) have attracted great interest for localized thermo-chemotherapy of cancer tissue/cells. From this perspective, smart polymeric electrospun NFs co-loaded with magnetic nanoparticles (MNPs) and a natural polyphenol anticancer agent, curcumin (CUR), were developed to enhance the local hyperthermic chemotherapy against melanoma, the most serious type of skin cancer. CUR/MNPs-loaded thermo-sensitive electrospun NFs exhibited alternating magnetic field (AMF)-responsive heat generation and "ON-OFF" switchable heating capability. Besides, corresponding to the reversible alterations in the swelling ratio, the "ON-OFF" switchable discharge of CUR from the magnetic NFs was detected in response to the "ON-OFF" switching of AMF application. Due to the combinatorial effect of hyperthermia and release of CUR after applying an AMF ("ON" state) for 600 s on the second and third days of incubation time, the viability of the B16F10 melanoma cancer cells exposed to the CUR/MNPs-NFs was reduced by 40% and 17%, respectively. Taken together, the macroscopic and nanoscale features of the smart NFs led to the creation of a reversibly adjustable structure that enabled hyperthermia and facile switchable release of CUR for eradication of melanoma cancer cells.