The interactions of nanoparticles (NPs) with “protein corona” and live cells are likely to become important in bionanoscience. These interactions play the central role in nanomedicine and nanosafety issues. The protein-adsorption layers located on the surface of colloidal NPs play an important role in their interaction with living cells, so characterization of the protein corona is of the utmost importance for understanding how exposure to NPs affects the biological responses of cells and organisms. This review deals with the interaction of NPs with proteins, live cells and organelles, and considers the proteomics analysis by which these interactions affect cytotoxicity. We offer an overview of the cytotoxicity of different NPs using proteomics analysis. We also review proteomics analysis of natural mineralo-protein NPs. Among the different approaches, proteomics analysis is simple, informative and cheap