The different structures of Ni-Mo/Al2O3 catalysts used in the secondary hydrogenation of coal-derived liquids were analyzed by the X-ray absorption fine structure (XAFS) method to clarify the catalyst deactivation mechanisms during the hydroprocessing. The XAFS analyses revealed the agglomeration of MoS2 crystallites, as well as the decomposition of the catalytically active ＇Ni-Mo-S＇ structure in the sampled catalysts. A greater amount of agglomeration was observed in the catalyst taken from the reactor exit as compared with the catalyst sampled at the inlet. Higher temperatures at the exit of the reactor presumably caused the enhanced agglomeration of the MoS2 crystallites. On the other hand, the changes observed in the local structure around Mo and Ni due to the decomposition of the Ni-Mo-S structure were pronounced in the catalyst sampled at the inlet. Preasphaltenes found in the coal-derived liquids were speculated as the most probable cause of the decomposition.