Molecular mechanics and semi-empirical quantum mechanical calculations were conducted to investigate the effect of water interaction on the Raman spectra of C60fullerene. It was found that the frequency of the fullerene surface modes Hg(7), A2g, and Hg(8) shifts to higher wavenumbers as the number of interacting water molecules increased. The Raman peak shift was non-linear and showed an intermediate plateau related to structural changes in the surrounding water molecules. The average C–C bond length was found to be essentially constant within 0.002 Å, indicating constant volume for the fullerene molecule. The current results confirm the suitability of C60 in applications as nanosensor to investigate liquid structures and transitions.