This project investigates the interaction between Importin 7 (Imp7), a nuclear transport receptor, and HIV-1 Integrase (IN), a viral enzyme essential for integration of viral DNA into the host genome. To characterize the molecular basis of this interaction, we performed hydrogen–deuterium exchange mass spectrometry (HDX-MS). The Imp7–IN complex was expressed, purified, and subjected to HDX under defined conditions, followed by pepsin digestion and LC-MS/MS analysis. TheHDX-MS results reveal the specific regions in Imp7 that interact with the C terminal of HIV-IN, providing mechanistic insights into their interaction. All raw HDX-MS data files, peptide identifications, and metadata are included in this submission.