Lignin is a renewable carbon resource to produce arenes due to its abundant aromatic structures. For the liquid-phase hydrodeoxygenation (HDO) based on metallic catalysts, the preservation of aromatic rings in lignin or its derivatives remains a challenge. Herein, we synthesized Mn-doped Cu/Al2O3 catalysts from layered double hydroxides (LDHs) for liquid-phase HDO of lignin-derived anisole. Mn doping significantly enhanced the selective deoxygenation of anisole to arenes and inhibited the saturated hydrogenation on Cu/Al2O3. With Mn doping increasing, the surface of Cu particles was modified with MnOx along with enhanced generation of oxygen vacancies (Ov). The evolution of active sites structure led to a controllable adsorption geometry of anisole, which was beneficial for increasing arenes selectivity. As a result, the arenes selectivity obtained on 4Cu/8Mn4AlOx was increased to be more than 6 folds of that value on 4Cu/4Al2O3 over the synergistic sites between metal Cu and Ov generated on MnOx.