Using density functional theory, noncovalent interactions and three mechanisms of covalent functionalization of troxacitabine anticancer drug onto γ-Fe2O3 nanoparticles have been investigated. Quantum molecular descriptors of noncovalent configurations were studied. It was specified that binding of troxacitabine onto γ-Fe2O3 nanoparticles is thermodynamically suitable. Hardness and the gap of energy between LUMO and HOMO of troxacitabine are higher than the noncovalent configurations, showing the reactivity of troxacitabine increases in the presence of γ-Fe2O3 nanoparticles. Troxacitabine can bond to γ-Fe2O3 nanoparticles through NH2 (k1 mechanism), OH (k2 mechanism) and CO (k3 mechanism) groups. The activation energies, the activation enthalpies and the activation Gibbs free energies of these reactions were calculated. It was specified that the and mechanisms are under thermodynamic control and the mechanisms is under kinetic control. These results could be generalized to other similar drugs.