To develop a green solvent for lignin dissolution, the most fundamental aspects of its mechanism must be elucidated. Understanding the thermodynamic behaviors is of significant importance for designing novel deep eutectic solvents (DESs) to dissolve lignin. Herein, the heat of dissolution of lignin in acidic, alkaline or neutral DESs was determined by high-precision solution microcalorimetry, and comprehensively investigated the effect of physicochemical properties of DESs on the heat of dissolution and solubility of lignin. The resulted observed that lignin dissolution in alkaline DESs was more vigorous exothermic than that in acidic and neutral DESs. The thermodynamic parameters for the dissolution of lignin in the DESs were calculated from the heat of dissolution and solubility. The positive free energy change indicated that the process of lignin dissolution was non-spontaneous and unfavorable thermodynamically. By analyzing the changes of enthalpy and entropy of lignin solution systematically, lignin dissolution in DESs was enthalpically favorable and controlled by the entropy term. Especially, the interaction entropy predominantly made the free energy change unfavorable for lignin dissolution. The achieved thermodynamic findings could serve as the basis to construct robust DESs for lignin biorefinery.