The optimal parameters of the chitosan-coated ferrofluid under two patterns of irradiation were investigated in this study. The quality characteristics were set both to the SAR (specific absorption rate, W/g) and the particle size (nm). The control factors were chosen as the gamma irradiation dose (Gy), the quantities of chitosan (g), and the molar ratio of Fe 3+ to Fe2+. It shows that SAR is a better choice for determining the quality characteristic. The quantities of chitosan have a less significant impact on SAR. The optimal condition for the Fe3+ /Fe2+ ratio was found to be between 2.0 to 2.5 when synthesizing the magnetite Fe3O4 cores. High dose (100 k Gy in this study) of gamma ray irradiation given only to the solid chitosan will have a significantly positive effect on SAR of the chitosan-coated ferrofluid for hyperthermia. However, high dose irradiation of the chitosan-coated ferrofluid tends to destroy the chitosan-magnetite cores bonds.