Fluorescent carbon dot (C-dot) nanoclusters composed of C-dot-loaded hollow silica spheres are obtained via the dehydration of mannose, which is adsorbed onto hollow silica spheres or poly(ethylene glycol)-graft-hollow silica spheres (PEG-g-hollow silica). The structure of C-dot nanoclusters are confirmed using 1H NMR, FTIR, TEM and TGA. C-dot nanoclusters show a redshifted fluorescence emission with an increased excitation wavelength. Passivation with PEG diamines improve the quantum yields to ∼2%. Confocal laser scanning microscopy (CLSM) results reflect the fact that C-dot nanoclusters can provide good cytoplasm imaging of live Hep G2 cells and live MCF-7 cells, and the imaging obtained is brighter and more even than those from free C-dots. With their combination of good photostability and low cytotoxicity, C-dot nanoclusters are promising for the production of higher quality bioimaging.