The interaction of difluoromethane (CH(2)F(2)) with the TiO(2) surface (P25 Degussa) at room temperature has been studied by Fourier-transform infrared spectroscopy for the first time. From the comparison between the adsorption characteristics and the gas-phase spectra it can be deduced that the molecule adsorbs through an acid-base interaction between one F atom and the surface Lewis acid site (Ti(4+)) and an H-bond between the CH(2) group and the surface Lewis basic site (OH(-) or O(2-)). In order to obtain more information about the orientation geometry and the variation of the molecular structural parameters, a quantum-mechanical investigation at DFT/B3LYP level has been also performed, considering the anatase (101) surface and focusing on the O(2-) as Lewis basic site. The resulting adsorbate-substrate structures involve the formation of an acid-base interaction between one F atom and the Ti(4+) ion and differ for the number of the involved H-bonds. According to the scaled vibrational frequencies, the simulated adsorption model which better agrees with the experimental data corresponds to that in which the CH(2) group interacts with the surface by only one H-bond.