Noncovalent functionalization of iron oxide nanoparticles (ION) with cytarabine anticancer drug (CYT) has been studied at B3LYP and M06-2X functionals using seven different configurations (ION/CYT1-7) and Fe-6(OH)(18)(H2O)(6) cluster model for ION. The energetic stability of seven noncovalent structures was determined by the calculation of adsorption energies. The AIM studies demonstrated that the noncovalent functionalization mainly occurs through intermolecular hydrogen bonds. The reaction between ION and CYT may produce seven different products (IONCYT1-7/H2O). The high barrier of IONCYT2/H2O (via CH2OH) product is lower than that of IONCYT3/H2O (via OH) product and therefore is the preferred pathway for covalent functionalization.