The hydrodeoxygenation of phenolics is one of the key processes in lignin upgrading to fuel or aromatic products. MoS 2 -based catalysts show potential application in this reaction, and the defects are known to play an important role in phenolic C− O bond activation. However, the preparation of defective MoS 2 -based catalysts is usually complex. In this work, we report a facile synthesis of highly defective MoS x O y catalysts from MoS 2 by the oxygen etching-reduction. With the increase in etching temperature, the structure evolution of catalysts goes through the 2D nanosheet, imperfect nanorod/nanotube to large bulk particle. After H 2 reduction, two types of defects are determined on the surface, including undercoordinated Mo 4+∼3+ from the MoS 2 phase and Mo 5+ from MoO x . The Mo 5+ site is found to be more effective than Mo 4+∼3+ in phenolic C−O activation, while the MoS 2 phase is stronger in H 2 dissociation than MoO x . On MoS x O y -350, MoS 2 and MoO x phases are intimately contacted in the nanoscale, leading to a synergistic effect between Mo 5+ and MoS 2 , thus showing the highest activity in the m-cresol HDO reaction.