Abstract: In this research work, spinel CuFe2O4 magnetic nanoparticles were synthesized by green microwave combustion method using leaf extract of Pedalium murex plant, then subsequently coated with TiO2 and rGO by sol–gel method. The obtained CuFe2O4@TiO2@rGO core@shell nanoparticles were examined for magnetic hyperthermia and cytotoxicity of human breast cancer cell line. X-ray diffraction, Fourier-transform infrared and EDX analyses confirmed the phase formation and formation of functional groups. The core shell nanostructure was elucidated by transmission electron microscopy. Magnetic measurements indicated the ferromagnetic behavior while the magnetic properties were strongly affected by the nature of coating layer, whereby the saturation magnetization decreased, and the hysteresis loop widened. Hyperthermia study indicated that the self-heating temperature is dose dependent, with a rise temperature range △T = 3–10 °C and specific absorption rate 20–100 W/g. Furthermore, a good cytotoxicity activity on Human Breast cancer cell line was achieved, with an IC50 = 26.07 ± 1.35 µg/mL. The designed CuFe2O4@TiO2@rGO nanostructure demonstrated great potential for magnetic hyperthermia and cytotoxicity against Human Breast cancer cell line.