Herein, flower-shaped hydrophilic superparamagnetic iron oxide nanoclusters (IONCs) are synthesized via one-pot thermolysis of iron acetylacetonate using triethanolamine (TEA) and diethylene glycol (DEG)/tetraethylene glycol (TTEG) mixtures at 9:1, 8:2 and 7:3 (v/v) ratios. The as-prepared 24–29 nm sized IONCs have displayed (i) saturation magnetization (Ms) values of ~68–78 emu/g, (ii) hydrodynamic diameters of ~95–192 nm and (iii) zeta potential values of +46 to +65 mV. Due to relatively high magnetization and water solubility, IONCs (prepared using 8:2 TEA:DEG, and 8:2 & 7:3 TEA:TTEG ratios) based aqueous ferrofluids i.e. NCAFF-1, NCAFF-2, and NCAFF-3 are investigated by calorimetric magnetic fluid hyperthermia (MFH) at 0.5–8 mg/ml concentrations by exposing them to the alternating magnetic fields (AMFs, H*f ~2.4–9.9 GA m−1 s−1). The NCAFF-3 has demonstrated excellent time dependent temperature rise (42 °C within 0.7–9.7 min) as compared to the NCAFF-1 and NCAFF-2. Moreover, the NCAFF-3 at 0.5 mg/ml concentration has exhibited enhanced heating efficacies with specific absorption rate (SAR) and intrinsic loss power (ILP) values of 142.4–909.4 W/gFe and 4.2–14.7 nHm2/kg, respectively. Furthermore, the NCAFF-3 has presented better cytocompatibility, and substantially reduced proliferation capacity of HepG2 cancer cells in in vitro MFH studies. Thus, the IONCs based ferrofluids (NCAFF-3) are very promising candidates for MFH therapeutics applications. © 2018 Elsevier B.V.