Research shows some potential applications for ionic liquids (ILs) with biomaterials. In this work, the ILs 1-butyl-3methylimidazolium tetrafluoroborate ([C(4)mim]BF(4)), 1-butyl-3-methylimidazolium chloride ([C(4)mim]Cl), 1-butyl-3-methylimidazolium bromide ([C(4)mim]Br), and 1,3-dimethylimidazolium iodine ([dmim]I) were employed to investigate their effects on the solubility of lysozyme in aqueous solutions at pH 4.5. The results demonstrate that lysozyme solubility increases with the addition concentration of [C(4)mim]BF(4) and [C(4)mimCl] and is nearly invariable with the increase of the [C(4)mim]Br concentration. Interestingly, the solubility slowly decreases with the increase of [dmim]I concentration. At constant added IL concentration, the solubility increases with increasing temperature. The effect of ILs on solubility can be attributed to changing interaction among lysozyme molecules. The effect of ILs employed in this work may provide crucial insight into the preparation of high-quality crystals and the development of new crystal forms as well as the design optimization of protein crystallization.