A series of halogen-free quaternary ammonium Brønsted acidic ionic liquids (ILs) were prepared and used for Biginelli reaction among aromatic aldehydes, urea or thiourea and β-dicarbonyl compounds. The influencing factors, such as the type and amount of catalyst, solvent, reaction time and reaction temperature, were investigated. The results demonstrated that the 3-(N,N-dimethylhexadecylammonium) propanesulfonic acid toluene sulfate ([DHPA][Tos]) provide the best catalytic activity, with good catalytic performance and reusability under solvent-free conditions. A possible mechanism that accounted for the [DHPA][Tos]-catalyzed reaction was proposed.