We report on the photoinduced decomposition of acetone on Zr- and Nb-doped anatase TiO2 nanoparticles prepared by the sol−gel method in oxygen-free environment (N2) and synthetic air, respectively. Physical properties of the nanoparticles were determined by TEM, SEM, AFM, XRD, and UV−vis spectroscopy. Photoinduced surface reactions were monitored by in situ Fourier transform infrared (FTIR) spectroscopy. Acetone photo-oxidation occurs in the absence of O2 in the reaction gas and is proposed to be due to reactions with photoactivated surface oxygen. In N2 atmosphere a new parallel reaction pathway is found that stimulates surface carbonate formation. A coupled diffusion-reaction model was developed to quantitatively determine the role of O diffusion. The results yield quantitative support to an oxygen surface diffusion mechanism, which depletes the surface from oxygen and gradually deactivates the particles in the absence of external oxygen supply. The diffusion reaction pathway is significant on the doped TiO2 particles. The contribution of this reaction pathway amounts to up to 65% of the total PID rate on Nb- and Zr-doped TiO2 in synthetic air environment, while it gives only a minor contribution on pure TiO2.