This is supplemental data of “ In-depth Profiling and Quantification of the lysine acetylome in Hepatocellular Carcinoma with a Trapped Ion Mobility Mass Spectrometer ” project. In this data, we employed an integrated proteomics and acetylomics strategy to characterize of three Huh7 cells (NC1, NC2, NC3) and three SIRT2 overexpression cells (SIRT2-1, SIRT2-2, SIRT2-3) with 4D proteomics technology. Proteomics analysis identified a total of 5052 proteins, of which 4255 proteins were quantified across all samples. A total of 5307 acetylation sites on 2094 proteins were identified.