Resonant energy transfer in hybrid CdSe quantum dot (QD) conjugated with Cy5-labelled molecular chaperone systems is observed with single molecule imaging technique. Photonic QDs are the core-shell type nanocrystals covered with organic surfactants on the outermost surfaces, i.e. CdSe/ZnS/TOPO's, and prefoldin (PFD) is used as prototype molecular chaperons. PFD is a jellyfish-shaped hexameric co-chaperone of group II chaperonins, which recognize hydrophobic portion of denatured proteins and encapsulate them within its central cavity. So the CdSe/ZnS/TOPO QDs can also be captured be cause of its surface similarity to the denatured proteins. We have found one possible reaction pathway to get such artificial complex in aqueous solutions with keeping bioactivities of the proteins. Performance of the complex is evaluated by TIRF imaging microscopy. As the proteins are transparent in visible wavelength region, labeling dyes, Cy5, which also work as acceptors, are connected to detect their behaviors microscopically. Forster type energy transfer is observed from the QD donors to Cy5-labeled PFD acceptors in single molecule level, which can be a distinct evidence for the complex formation. (C) 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim