Facing the challenge of processes in direct coal liquefaction (DCL), it is vital to develop optimal hydrogen-donor solvent (H-donor) to dramatically moderate coal liquefaction conditions. Here, we propose an approach for rational design of optimal H-donor candidates based on density functional theory (DFT) calculations combining reverse searching algorithm. First, the mechanism of hydrogen transfer from H-donor to coal radical was investigated by using common model compounds. DFT calculations show that the concerted hydrogen transfer route promoted by coal radicals is the dominant pathway. The C-H bond dissociation enthalpies (BDEs) show strong correlation with intrinsic reaction barriers and rate constants (in log scale), which allow us to define a cheap metric for comparing the hydrogen-donation ability of different H-donors. Then the framework for rational design of H-donor candidates is established to seek molecules with low C-H BDEs based on inverse molecular design strategy. In the searching procedure, the chemical structure of parent molecule is varied by appropriate substituent from a predefined library (15 substituents). To reduce searching space, four empirical rules are proposed to guide the structural modifications. Finally, the H-donor candidates designed are validated by transition state calculations. It is confirmed that the inverse molecular design approach is effective for seeking candidate H-donors with lower reaction barriers and potentially higher rate of hydrogenation, which open a window for the rational design of optimal H-donors to improve the yields of the liquid products from coal under mild conditions.