Hydroxyl radical protein footprinting (HRPF) is a mass spectrometry (MS)-based method for studying protein structures, interactions, conformations, and folding. We evaluated dimethylthiourea (DMTU) as a replacement for catalase in quenching HRPF reactions. We observed that the DMTU is highly effective at quenching HRPF oxidation. DMTU does not cause background protein issues like catalase, resulting in an increased number of protein identifications from complex mixtures.