Compared to animal cells, the study of mechanical properties of living plant cells received much less attention. Quartz crystal microbalance (QCM) is a non-invasive and label-free interfacial sensor technique capable of studying viscoelastic properties of living cells which has been applied to different types of animal cells [1,2]; however, it has not been applied to plant cells yet. In this work, we applied the QCM with Dissipation (QCM-D) technique for the study of living tobacco BY-2 Cells. BY-2 cells were immobilized on the positively charged poly(diallyl dimethyl ammonium chloride) (PDADMAC)/SiO2 QCM electrode at a certain concentration of mannitol solution, frequency shift (ΔF) and dissipation change (ΔD) were monitored under different overtones (n). The results showed that both ΔDn0.5 and ΔF/n0.5 are not constants for different overtones indicating the viscoelastic feature of living BY-2 cells. Then the solution was replaced with different mannitol concentrations subsequently. We used the cell viscoelastic index (CVI) (CVI=ΔD/ΔF) [3] to characterize the viscoelastic properties of BY-2 cells under different osmotic conditions. The mannitol concentration that induced initial plasmolysis (Cip) for BY-2 cells is around 0.3 M. When the mannitol concentration (CM) is above Cip, CVI decreased with the increase of CM indicating that the cells became softer, whereas when CM < CiP, the change trend of CVI with CM became more complicated .since cell wall and protoplast both contribute to the QCM responses. The QCM results were discussed with the morphological changes for the BY-2 cells immobilized on PDADMAC modified glass slides observed by an optical microscopy.