Forster resonance energy transfer (FRET) between quantum dot (QD) donors and red fluorescent protein (RFP)-tagged integrin acceptors in live cells is reported for the first time. A silica microsphere was coated with CdSeZnS QDs and mounted to the cantilever of an atomic force microscope (AFM). The QD microsphere is then conjugated with fibronectin to bind with RFP-alphav integrins expressed on the surface of HeLa cells. Following AFM-controlled cell contact with the QD-microsphere structure, FRET is observed between the QD-RFP pair using a photobleaching measurement technique. This FRET probe technique provides a novel tool for studying the cell surface receptor-ligand interactions in biomedical and biological research.