In this report, we assessed the importance of internal microstructure on TiO2-containing cement-based mortars during the degradation of NOx gases through a photocatalytic oxidation process. Six samples of mortar containing the same amount of cement (14%) and TiO2 (1%) were prepared by changing the amount and type of sand used in their formulation, as well as the water/cement ratio, thus yielding mortars with different overall porosities and pore size distributions. The particle size distribution of the raw materials had a strong influence on the final microstructure of the hardened products. The volume of macropores (in this study, pores with diameter larger than 80 nm), which appeared according to the size of particle used in the mortar preparation and the extent of the hydration reaction of the cementitious compounds, was related to the presence of active sites accessible to the photocatalytic oxidation (PCO) process. Samples with large macropore volume and lower amount of hydration products exhibited the highest PCO efficiency. Taking into account the low weight-percent of TiO2, the PCO performance was found to be outstanding, with NO conversion values generally larger than 20%. Moreover, the microstructure was related to the amount of TiO2 present in the mortar surface.