ABSTRACT: Lysine acetylation (Kac) plays a critical role in the regulation of a great deal of important cellular processes. However, little is known about Kac in Solenopsis invicta, which is one of the 100 most dangerous invasive species in the world. Lysine acetylome in S. invicta was evaluated for the first time in this study. Altogether, 2387 Kac sites were tested in 992 proteins. The prediction of subcellular localization indicated that most identified proteins were located in cytoplasm, mitochondria and nucleus. The enriched Kac site motifs included Kac H, Kac Y, Kac G, Kac F, Kac T, and Kac W. H, Y, F, and W were of frequent occurrence at the +1 position, whereas G, Y and T were of frequent occurrence at the –1 position. Based on cellular component, acetylated proteins were enriched in cytoplasmic part, mitochondrial matrix, and cytosolic ribosome. Furthermore, 25 pathways were detected to be significantly enriched. Interestingly, arginine and proline metabolism as well asphagosome, which were related to immunity, contained several Kac proteins. Acetylation or deacetylation of the proline and phagosome proteins may adjust the protein function, which may be why S. invicta was highly immune. As for interaction network investigation, diverse interactions were adjusted by Kac. Our study of lysine acetylome supplies abundant information for function analysis of reversible Kac in the growth and development of S. invicta and other Hymenoptera insects. Confirming the functions of Kac target proteins may be useful to design specific and effective drugs to prevent and control this dangerous invasive species.