Updated project metadata. A combination of covalent labelling techniques and mass spectrometry (MS) is currently a progressive approach for the de-riving insights relating to the mapping of protein surfaces or protein-ligand interactions. In this study, we mapped an interac-tion interface between DNA binding domain (DBD) of FOXO4 protein and DNA binding element (DAF16) using the Fast Photochemical Oxidation of Protein (FPOP). Residues involved in protein – DNA interaction were identified using bottom-up approach. To avoid a misinterpretation of obtained data, caused by possible multiple radical oxidation leading to the alter-ing a protein surface and oxidation of deep-buried amino acid residues, a top-down approach was employed for the first time in FPOP analysis. An isolation of singly-oxidized ions allowed their gas-phase separation from multiply oxidized species followed by CID and ECD fragmentation. Application of both fragmentation techniques allowed to obtained complemen-tary fragment sets, out of which the regions shielded in the presence of DNA were deduced. The results obtained by bottom-up and top-down approaches were in a high consistency. Lastly, FPOP results were compared with HDX study of FOXO4-DBD•DAF16 complex. No contradictions were found between both methods. Moreover, their combination provide com-plementary information related to the structure and dynamics of the protein-DNA complex.