Gold nanoclusters are emerging as new materials for biomedical applications because of promises offered by their ultrasmall size and excellent biocompatibility. Here, the synthesis and optical and biological characterizations of a highly luminescent folate-functionalized Au cluster (Au -FA) are reported. The Au -FA clusters are synthesized by functionalizing the surface of Au (SG) clusters, where SG is glutathione, with benzyl chloroformate and folate. The functionalized clusters are highly water-soluble and exhibit remarkably bright luminescence with a quantum yield of 42%, significantly higher than any other water-soluble gold clusters protected with thiolate ligands. The folate groups conjugated to the gold cluster give rise to additional luminescence enhancement by energy transfer sensitization. The brightness of Au -FA is found to be 4.77 mM cm , nearly 8-fold brighter than that of Au (SG) . Further biological characterizations have revealed that the Au -FA clusters are well-suited for bioimaging. The Au -FA clusters exhibit excellent photostability and low toxicity; nearly 80% cell viability at 1000 ppm of the cluster. Additionally, the Au -FA clusters show target specificity to folate-receptor positive cells. Finally, the time-course in vivo luminescence images of intravenous-injected mice show that the Au -FA clusters are renal-clearable, leaving only 8% of them remained in the body after 24 h post-injection.