As a representative nanomaterial, C₆₀ and its derivatives have drawn much attention in the field of drug delivery over the past years, due to their unique geometric and electronic structures. Herein, the interactions of hydroxyurea (HU) drug with the pristine C₆₀ and heterofullerene MC₅₉ (M = B, Si, Al) were investigated using the density functional theory calculations. The geometric and electronic properties in terms of adsorption configuration, adsorption energy, Hirshfeld charge, frontier molecular orbitals, and charge density difference are calculated. In contrast to pristine C₆₀, it is found that HU molecule is chemisorbed on the BC₅₉, SiC₅₉, and AlC₅₉ molecules with moderate adsorption energy and apparent charge transfer. Therefore, heterofullerene BC₅₉, SiC₅₉, and AlC₅₉ are expected to be promising carriers for hydroxyurea drug delivery.