Protein ubiquitination is a crucial post-translational modification that regulates diversecellular processes, including protein degradation and signal transduction. This study employs proteomic and ubiquitinomic analyses to systematically profile the alterations in protein expression and ubiquitination sites in Huh7 cells after treatment with 10 µM DUBTAC A1.We utilized high-resolution tandem mass spectrometry (LC-MS/MS) followed by extensive bioinformatic analysis. The dataset comprises raw mass spectrometry data, processed search results including protein identification and quantification, and a comprehensive list of identified ubiquitination sites. Our data provides a valuable resource for understanding the crosstalk between proteomic and ubiquitinomic alterations. This repository contains the complete proteomic and ubiquitinomic dataset supporting the findings of the related manuscript.