Palladium(II) complexes coordinated to large planar amine ligands represent a lead structure of considerable interest in current antitumor drug design. However, the question is whether these complexes can bind to DNA bases affording bifunctional adducts for great steric hindrance provided by the bulky ligands. We studied the interaction of the palladium(II) complex, PdCl2L2, where L was 2-hydroxypydridine, with DNA bases using density functional theory and combining with isoelectric focusing polarized continuum (IEF-PCM) solvation model. Activation free energies for the complex monofunctional and bifunctional binding to DNA bases were lower than those for platinum-based antitumor agents. All reactions under study were exothermic in aqueous solution. The results indicate that the large planar amine ligands in the palladium complexes do not hinder formation of bifunctional adducts with DNA bases, and the rates for monofunctional and bifunctional binding to DNA bases to be larger than those of platinum-based agents.