AbstractThis work focused on the solution-sensitivity and the comprehensive mechanism of lignin breakdown during the phosphoric acid-acetone pretreatment process using density functional theory calculations. The structures and properties of a-O-4 lignin, β-5-3 lignin, and β-βlignin were detected, which showed that the bond length follows the order: a-O-4 bond < β-5-3 bond < β-βbond, but a-O-4 lignin is more sensitive to solvent molecule thanβ-β lignin and β-5-3 lignin. The decomposition mechanism of a-O-4 lignin, β-5-3 lignin, and β-β lignin in different solutions showed that a-O-4 lignin decomposes much more easily than β-5-3 lignin and β-β lignin, acting as the most accessible and susceptible point of lignin. Further, the selectivity of decomposition of lignin depends markedly on the synergy of solution and position. The physical origin of the structure-selectivity of lignin in different solution can be rationalized in terms of both thermodynamics and kinetics. The reactions investigated in this work constitute a large database for understanding the chemistry of a-O-4 lignin, β-5-3 lignin, and β-βlignin, and their decomposition in different solutions.