This works aims to present a preliminary study about the application on painting of TiO2 nanoparticles for self-cleaning and protective purposes. We firstly assessed the photocatalytic activity of the TiO2 nanoparticles, obtained by Pulsed Laser Ablation, by the discoloration of dye. After, the colloidal dispersion is applied to painting samples prepared in laboratory, according to old recipes and using the most-used historical binders and pigments, in order to verify the cleaning efficiency by discoloration of the chromatic markers. The spectrophotometric analysis is performed studying the Spectral Reflectance Factor trend and the color coordinates.