Iron oxide nanocrystals (IONCs) are appealing heat mediator nanoprobes in magnetic-mediated hyperthermia for cancer treatment. Here, specific absorption rate (SAR) values are reported for cube-shaped water-soluble IONCs prepared by a one-pot synthesis approach in a size range between 13 and 40 nm. The SAR values were determined as a function of frequency and magnetic field applied, also spanning technical conditions which are considered biomedically safe for patients. Among the different sizes tested, IONCs with an average diameter of 19 ± 3 nm had significant SAR values in clinical conditions and reached SAR values up to 2452 W/gFe at 520 kHz and 29 kAm–1, which is one of the highest values so far reported for IONCs. In vitro trials carried out on KB cancer cells treated with IONCs of 19 nm have shown efficient hyperthermia performance, with cell mortality of about 50% recorded when an …