The aim of this paper is to study the effect of gamma-rays on structural, physicochemical, optical and photo-catalytic performance of TiO2 nanoparticles doped with different concentrations of copper ranging from 0 to 6 at.%. The powders have been prepared by sol-gel technique and annealed at 400 degrees C. They were irradiated by gamma-rays with doses varying from 14 to 60 KGy. These investigations confirm the formation of anatase TiO2 nanoparticles and Cu2+ ion substitution for Ti4+ sites within the TiO2 structure. This study also shows that, once the TiO2 structure is saturated with copper, a metallic copper segregation is formed at the crystallite surfaces. After gamma irradiation, samples present a crystalline core and a disordered shell structure as a result of the formation of oxygen vacancies. Such oxygen vacancies at the TiO2 nanocrystal surface lead to a remarkable enhancement of the photocatalytic activity of Cu-doped TiO2 catalysts.