Purpose: To eliminate CD44, a putative cancer stem cell (CSC) marker, overexpressing head and neck squamous cell carcinoma (HNSCC) cells by using hyaluronan-conjugated, dextran-coated super paramagnetic iron oxide nanoparticles (HA-DESPIONs), in conjunction with induced heat produced by exposure to an alternating magnetic field (AMF). Methods: An AMF generator was constructed by means of a solenoid coil and an impedance circuit driven by a power amplifier. A signal generator produced a small sinusoidal signal of 130 kHz that was then amplified to 9 A (peak to peak value) to generate an AMF of approximately 10 kA/m (12.6 mT) at the center of a coil. The heat generating effect of the AMF generator was tested via several kinetic and dose-dependent bulk heating experiments by exposing readily available magnetic nanoparticles to AMF. For elimination of CD44 population, UT-SCC-14 cells were exposed to either targeted HA-DESPIONs or non-targeted DESPIONs at a concentration 200 μg/ml and exposed to AMF for 30 minutes. Cells were processed after 24 hours for flow cytometry based analysis of apoptosis. Results: Magnetic nanoparticles caused a concentration-dependent bulk heating effect in response to AMF resulting in a significant temperature rise. Following the exposure to AMF, non-conjugated DESPIONs were unable to induce targeted hyperthermia and hence had no effect on CD44 cell death in HNSCC cells. However, there was a significant cell death in the CD44 population treated with HA-DESPIONs and exposed to AMF. This effect was only obeserved when the magnetic field was turned on. Conclusion: Bulk heating experiments concluded that a simple AMF generator was able to activate magnetic nanoparticles and flow cytometry demonstrated that HA-DESPIONs were able to cause apoptosis in UT-SCC-14 cells that express CD44.This may be a promising strategy to specifically target cancer stem cells (CSCs) for the treatment of HNSCC.