The direct cleavage of C−O bonds in lignin and its derivatives via hydrogenolysis is an essential reaction process for lignin conversion. Herein, we design a MgAl2O4 supported Ru catalyst using a facile and green method involving ball milling and microwave heating. The optimal catalyst, 0.5Ru/MgAl2O4, displayed enhanced catalytic performance for 4−O−5 linkage scission compared to 0.5Ru/Al2O3 and 0.5Ru/MgO, achieving a tuenover frequency of 352.9 h−1 for diphenyl ether (DPE) conversion. 0.5Ru/MgAl2O4 with low Ru loading achieved complete conversion of DPE, with 43.8% yield of cyclohexane (CHE) and 42.6% yield of cyclohexanol (CHL) after 2 h at 160 °C and 1.5 MPa H2. The promising catalytic activity can be attributed to the abundant electron-rich Ru0 species with high dispersion formed on MgAl2O4, derived from the strong electron transfer from the support to Ru. The reaction mechanism for the direct cleavage of the 4−O−5 bond, followed by phenyl ring hydrogenation, was confirmed by rigorous experiments. This work provides an inspiring idea for developing efficient heterogeneous catalysts for the utilization of lignin resources via hydrogenolysis.