Updated project metadata. Here, we aimed to compare two of the most commonly used global proteomics strategies, label-free quantification (LFQ) and tandem mass tag-based quantification (TMT) to identify the most suitable tool for toxicology research questions on the systemic level. Using a biological case study of HepG2 exposure to benzo[a]pyrene (BaP), we uncovered the advantages and limitations of the two strategies from the view of proteome coverage, fold changes, significant numbers of proteins, and pathway alterations.