Identification of proteins especially at low concentrations or with post-translational modifications is important in the biomedical and clinical research.Development of micro/nano analytical devices has attracted interest in the applications.Here we introduce the microfluidic chips or macroporous silica as reactors for highly efficient and controllable proteolysis.The ordered mesoporous matrices tailored by pore size and surface charge have been used as nanoreactors to favor the efficient protein digestion inside the mesochannels.The biological complex samples extracted from the cytoplasm of human liver tissue was further studied.We have also developed the multi-functional nanoreactors based on the surface modification of mesoporous silica materials for the integrated analysis of phosphoproteins and glycoproteins,respectively.Furthermore,a droplet-based proteolysis reactor has been developed to fractionate proteins separated by HPLC for an on-line digestion and identification by ESI-MS/MS.Such droplet proteolysis was an approach to interface protein separation and peptide mass spectrometry analysis.