Selective cleavage of C−O bonds in diphenyl ether (DPE), a lignin-derived 4-O-5 linkage, is a challenging topic and of great significance to produce value-added aromatic products for sustainable future. Activated carbon (AC) with different pore structures has different catalytic effects on the reaction. Herein, Ni catalysts supported on AC-1, AC-2, and AC-3 with specific surface area (SSA) values of 829, 1731, and 2399 m 2 /g, respectively, were investigated in the hydrogenolysis and hydrolysis of DPE. The proper pore structure of AC facilitates the entry of reactants and promotes the reaction. AC with a larger SSA and stronger hydrophilicity was more conducive to metal dispersion and water adsorption to promote the hydrogenolysis/hydrolysis of DPE. The apparent activation energy (E a ) and the turnover frequency further demonstrated that Ni/AC-3 possessed the highest catalytic activity compared to Ni/AC-2 and Ni/AC-1. Catalytic hydrogenolysis/hydrolysis of DPE can be therefore achieved over Ni/AC-3 under mild conditions (180 °C and 1 MPa H 2 ), which is highly selective to afford cyclohexane and cyclohexanol as the major products with the selectivities of 35.5 and 63.9%, respectively. The application of a hydrophilic Ni/AC catalyst with a high SSA may provide a promising approach for the valorization of lignin-derived fragments.