The separation of thorium and uranium is an important guarantee for the fuel cycle of thorium-based molten salt reactors. Benzoxazole-based ligands have a wide range of applications and are also potential ligands for actinide separation. In this work, density functional theory (DFT) calculations were used to study the intrinsic properties of two ligands, 2,6-bis(benzo[d]oxazole-2-yl)pyridine (ligand a) and 1-(6-(4-acetylbenzo[d]oxazol-2-yl)pyridin-2-yl)ethan-1-one (ligand b), revealing the structural characteristics and complexation behavior of their complexes with Th⁴⁺/UO₂²⁺. Quantum theory of atoms in molecules (QTAIM) and extended transition state - natural orbitals for chemical valence (ETS-NOCV) analyses show that the ligands form classical coordination bonds with Th⁴⁺/UO₂²⁺, with M−N_oz bonds stronger than M−N_py bonds and partial electron acceptance by carbonyl O. The thermodynamic properties were used to evaluate the separation performance of these ligands for Th⁴⁺/UO₂²⁺ in four solvents (water, 1-hexanol, n-octanol and n-dodecane), with L_a more suitable for back extraction process and L_b having stronger binding with Th⁴⁺/UO₂²⁺. This work provides valuable theoretical insights into Th⁴⁺/UO₂²⁺ separation based on benzoxazole.