The identification of protein modification sites and the identification of heterogeneity are the key links in the quality control of modified proteins, especially the analysis of PEGylation sites and identification of PEGylation heterogeneity are related to the pharmacokinetics, pharmacodynamic properties and stability of protein drugs. Therefore, the analysis of PEGylation sites and identification of PEGylation heterogeneity are important biochemical technologies in the research and development of polyethylene glycol modified protein drugs. MALDI-TOF MS and ESI-MS technology methods can be used to analyze of PEGylation sites and identify the PEGylation heterogeneity of drug proteins.