We introduce IC-FPOMP (in-cell fast photochemical oxidation of MPs), a method enabling in situ footprinting of IMPs within live cells. IC-FPOMP generates reactive oxygen radicals from several precursors nearby the membrane. We achieve high-throughput and rapid footprinting of IMPs. IC-FPOMP of two human IMPs (human glucose transporter-hGLUT1 and human gamma glutamyl carboxylase-hGGCX) were successful, providing comprehensive footprinting of both the transmembrane and extramembrane regions. IC-FPOMP offers insights on IMP structure-function relationships in cell for the first time, facilitating drug discovery.