Ionic liquids (ILs) have shown potentials as a new reaction medium for biocatalysis, either as such or as an aqueous mixture. Their unique ionic nature is important in affecting the enzyme performance, and the Hofmeister effects provide a reasonable explanation for this. In this review, the impact of Hofmeister effects on enzyme performance in aqueous solution was first examined, concerning the specific ion effects on altering the bulk water properties, modifying the protein-water interactions, and interacting with the enzyme molecules; then the effect of IL cations and anions on enzyme activity and stability in aqueous IL mixtures was discussed, taking both kinetic and structural studies into consideration; and finally, our recent study regarding mushroom tyrosinase in the presence of ILs and their associated anions was used to illustrate the cooperative functioning of IL cations and anions in affecting enzyme performance, following the Hofmeister series. Design and use of water-mimicking ILs composed of chaotropic cations and kosmotropic anions may facilitate the applications of ILs in biotransformations.