Cultured human Huh-7 cells were infected with SARS-CoV-2 and harvested after 24, 48 and 72 h. The extracted proteins were processed in triplicates preparing for mass spectrometric analysis. Data acquisition was completed, including control samples of non-infected cells, following isobaric tandem mass tag (TMT) chemical labeling and on-line fractionation of the 12 combined biological replicates. The resulted vendor specific raw files (Thermo Scientific) of 12 fractions are provided. The data is further analyzed in order to identify regulated proteins upon SARS-CoV-2 infection to understand the underlying biological processes through pathway analysis. Additional details about the study is going to be completed in the manuscript already submitted for publication.