Post-translational modification of proteins is a key step in the process of regulating their biological functions and it's an important molecular basis in the dynamic response and interaction of proteins, meanwhile, it can be considered as important targets to regulate the cell signaling networks. At present, post-translational modification of protein has become a critical area in the research of proteins. In prokarytes, post-translational modification of proteins can play a crucial role in the life activities, such as cell signal transduction, metabolism, protein degradation, pathogenicity of pathogenic microorganisms and so on. The types, mechanisms and functions of the classical post-translational modification of proteins in prokaryotes were summarized and the recently discovered global acetylation in Salmonella enterica, as well as the ubiquitin-like modification in Mycobacterium tuberculosis, were also introduced.