A systematic study of microwave-assisted degradation of lignin model compounds such as benzyl phenyl ether (BPE) and guaiacol, in imidazolium-based ionic liquids, was performed by evaluating the catalytic activity of 29 types of ionic liquids as both solvent and catalyst. After measuring and comparing the acidity of each ionic liquid solution for BPE and guaiacol degradation under the microwave irradiation and conventional heating conditions, it was found that the ionic liquid 1-butyl-3-methylimidazolium hydrogen sulfate ([BMIM]HSO4) was the most effective for decomposing the lignin model compounds. The experimental results indicate that ionic liquid acidity is in favor of the catalytic activity for BPE and guaiacol degradation, microwave irradiation could accelerate the degradation rate by 650% for BPE and 1120% for guaiacol and significantly increase the reaction selectivity. It was also found in experiments that the ionic liquid [BMIM]HSO4 could be used for 5 times without any loss of catalytic activity. The possible mechanisms for BPE and guaiacol degradation are proposed based on the product distributions.