Acetylation is a reversible post-translational modification of proteins mediated by acetyltransferases and deacetylase. Acetyltransferase engages in transferring the acetyl moiety of acetyl-CoA to the amino acid residue of the substrate protein, and the acetyl moiety of protein is removed by deacetylase. Acetylation is involved in the regulation of many basic biological processes, acting on histones and non-histone proteins, thus affecting a series of cellular processes such as gene transcription, regulating mRNA stability, mediating protein localization and degradation, etc. More and more studies have shown that protein acetylation plays an important role in the pathogenic process of pathogenic bacteria. Legionella pneumophila (L. pneumophila) is an intravacuolar pathogen that can cause acute pneumonia in susceptible human hosts. L. pneumophila can be airborne to infect macrophages in human lung tissue. Successful intracellular survival in hosts depends on the formation of the specialized Legionella-containing vacuolar (LCV). Upon invading host cells by phagocytosis, more than 300 different effectors are delivered into host cells via the Icm/Dot type IV system (T4SS) into host cells. These effectors hijack a variety of host cellular processes by diverse mechanisms, redirecting components of the host cell secretory pathway to remodel and maturate the LCV, and play an extremely important role in L. pneumophila survival and replication in host. Chief among them are mediated the post-translational modification that perturb host signal pathway. Among L. pneumophila effectors are quite a bit proteins that show primary amino acid sequence homology to eukaryotic GNAT family acetyltransferases or prokaryotic serine/threonine acetyltransferases. This article mainly reviews acetylation modification, the pathogenic mechanism of L. pneumophila, and the role of acetylation in the pathogenic process of the pathogen and highlights the known virulence as acetyltransferase and their role in host interaction, providing a reference for understanding the mechanism of acetylation modification in the pathogenic process of L. pneumophila.