Hyperthermia is one of the promising treatments for cancer therapy. However, the development of a magnetic fluid agent that can selectively target a tumor and efficiently elevate temperature while exhibiting excellent biocompatibility still remains challenging. Here a new core-shell nanostructure consisting of inorganic iron oxide (Fe 3 O 4 ) nanoparticles as the core, organic alginate as the shell, and cell-targeting ligands (ie, D-galactosamine) decorated on the outer surface (denoted as Fe 3 O 4 @Alg-GA nanoparticles) was prepared using a combination of a pre-gel method and coprecipitation in aqueous solution. After treatment with an AC magnetic field, the results indicate that Fe 3 O 4 @Alg-GA nanoparticles had excellent hyperthermic efficacy in a human hepatocellular carcinoma cell line (HepG2) owing to enhanced cellular uptake, and show great potential as therapeutic agents for future in vivo drug delivery systems.