A smart hyperthermia nanofiber is described with simultaneous heat generation and drug release in response to ‘on-off’ switching of alternating magnetic field (AMF) for induction of skin cancer apoptosis. The nanofiber is composed of a chemically-crosslinkable temperature-responsive polymer with an anticancer drug (doxorubicin; DOX) and magnetic nanoparticles (MNPs), which serve as a trigger of drug release and a source of heat, respectively. By chemical crosslinking, the nanofiber mesh shows switchable changes in the swelling ratio in response to alternating ‘on-off’ switches of AMF because the self-generated heat from the incorporated MNPs induces the deswelling of polymer networks in the nanofiber. Correspondingly, the ‘on-off’ release of DOX from the nanofibers is observed in response to AMF. The 70% of human melanoma cells died in only 5 min application of AMF in the presence of the MNPs and DOX incorporated nanofibers by double effects of heat and drug. Taken together these advantages on both the nano- and macroscopic scale of nanofibers demonstrate that the dynamically and reversibly tunable structures have the potential to be utilized as a manipulative hyperthermia material as well as a switchable drug release platform by simple switching an AMF ‘on’ and ‘off’.