Magnetic nanoparticles have an important role as heat generators in magnetic fluid hyperthermia, a type of nextgeneration cancer treatment. Despite various trials to improve the heat generation capability of magnetic nanoparticles, iron oxide nanoparticles are the only approved heat generators for clinical applications, which require a large injection dose due to their low hyperthermia efficiency. In this study, iron oxide nanoclusters (NCs) with a highly enhanced hyperthermia effect and adjustable size were synthesized through a facile and simple solvothermal method. Among the samples, the NCs with a size of 25 nm showed the highest hyperthermia efficiency. Differently sized NCs exhibit inconsistent interparticle crystalline alignments, which affect their magnetic properties (e.g., coercivity and saturation magnetization). As a result, the optimal NCs exhibited a significantly enhanced heat generation efficiency compared with that of isolated iron oxide nanoparticles (ca. 7 nm), and their hyperthermia effect on skin cancer cells was confirmed.