In the present study we implemented the bioUb approach to identify DUB substrates in a systemic manner. DUBs have been individually silenced so that the ubiquitination levels of their respective substrates are increased, and hence, upon isolation, susbtrates have been detected by mass spectrometry. Here we report quantitative proteomic data of the putative substrates of 5 human DUBs: USP1, USP7, USP9X, USP11 and USP42.