Updated publication reference for PubMed record(s): 30988469. We report the discovery of a photo-cleavable anionic surfactant, 4-hexylphenylazosulfonate (Azo) that can be rapidly degraded upon UV irradiation, for top-down proteomics. Azo can effectively solubilize proteins with performance comparable to SDS and is mass spectrometry (MS)-compatible. Azo-aided top-down proteomics allowed the detection of 100-fold more unique proteoforms and enabled the solubilization of membrane proteins for comprehensive characterization of post-translational modifications. Azo is simple to synthesize in large quantity for general use as an SDS replacement.