This study develops a reliable aqueous-phase method for the synthesis of CdSeS/ZnS core/shell QDs employing microwave irradiation technique. Firstly, CdSeS core QDs were produced by heating a precursor solution containing Cd2+, 3-mercaptopropionic acid (MPA) and Na2SeSO3 at 130 °C for 30 min. After purification through centrifugation, the CdSeS core QDs were successfully capped with a ZnS shell through heating a capping solution containing Zn2+, S2– and MPA at 100 °C for 1 h. Both the core/shell QDs and core QDs were characterised by X-ray powder diffraction, transmission electron microscopy and X-ray photoelectron spectroscopy, and the epitaxial growth of a ZnS shell on the surface of CdSeS QDs was confirmed. The prepared CdSeS/ZnS core/shell QDs showed significantly enhanced luminescence and photostability than that of CdSeS core QDs. Finally, the CdSeS/ZnS core/shell QDs were applied to image live Hela cells. The pilot experiments showed that the cells were successfully stained and exhibited bright green fluorescence. The small size QDs were localised predominantly in the nuclear compartment of Hela cells with negligible cytotoxicity, even at a concentration of 300 μg mL−1 after 24 h incubation. Our results suggest that the new core/shell QDs could be highly biocompatible and have wide applications in biolabelling and imaging.