Small ubiquitin-related modifier (SUMO) exists widely in all eukaryotic cells, which is involved in many signal transduction and metabolism pathways. Systematic identification of SUMOylated proteins is helpful to reveal the function and mechanism of SUMOylation from an overall perspective. At present, it is difficult to identify the SUMOylation sites, and how to study the SUMOylated proteins on a large scale has not been determined. This paper systematically analyzes the proteomic studies of protein SUMOylation in mammalian cells. On the basis of summarizing the research methods and achievements, the mutation mode and enrichment mode of SUMO are analyzed in detail, and then the ideal methods for systematic identification of SUMOylation sites in cells and tissues are concluded.