The influence of high hydrostatic pressure on the structure and protein-protein interaction potential of highly concentrated lysozyme solutions up to about 370 mg ml−1 was studied and analyzed using small-angle X-ray scattering in combination with a liquid-state theoretical approach. In the concentration region below 200 mg ml−1, the interaction parameters of lysozyme solutions are affected by pressure in a nonlinear way, which is probably due to significant changes in the structural properties of bulk water, i.e., due to a solvent-mediated effect. Conversely, for higher concentrated protein solutions, where hydration layers below ∼4 water molecules are reached, the interaction potential turns rather insensitive to compression. The onset of transient (dynamic) clustering is envisaged in this concentration range. Our results also show that pressure suppresses protein nucleation, aggregation and finally crystallization in supersaturated condensed protein solutions. These findings are of importance for controlling and fine-tuning protein crystallization. Moreover, these results are also important for understanding the high stability of highly concentrated protein solutions (as they occur intracellularly) in organisms thriving under hydrostatic pressure conditions such as in the deep sea, where pressures up to the kbar-level are reached.