Nucleation is a critical step determining the outcome of the entire crystallization process. Finding an effective nucleant for protein crystallization is of utmost importance for structural biology. The latter relies on good quality crystals to solve the three-dimensional structures of macromolecules. In this study we show that crystalline barium sulfate (BaSO4) with an etched and/or ionic liquid (IL) functionalized surface can (1) induce protein nucleation at concentrations well below the concentration needed to promote crystal growth at control conditions, (2) can shorten the nucleation time, (3) increase the growth rate, and, finally, (4) may help to improve the protein crystal morphology. These effects were shown for lysozyme, RNase A, trypsin, proteinase K, myoglobin and hemoglobin. Therefore, the use of BaSO4 particles enable us saving on the protein amount on crystallization trials and increase the chance of obtaining protein crystals of desired quality. In the context of the underlying mechanism, it is shown that the protein - solid contact formation is governed by the interaction of the polar compartments of the biomacromolecule with the support. The tendency of a protein to concentrate near the solid surface is enhanced by both the hydrophobicity of the protein and that of the surface (tuned by the functionalizing ILs). These mechanisms of interaction of biomacromolecules with inorganic hydrophilic solids correspond to the principles of amphiphilic IL-mineral interactions.