Non-selectivity of TiO2-based photocatalysis is a known drawback of this technology for full scale water treatment applications. It results in significant decline in decomposition of toxic target contaminants when other non-toxic organic compounds such as natural organic matter (NOM) compete in the reaction. Previously, size exclusion of large NOM onto the mesoporous structure of TiO2 photocatalyst was proven to improve the selective decomposition of small size target chemicals. In this study, manipulation of reaction pH as a crucial parameter in governing the adsorption and decomposition of organic chemicals was combined with the size exclusion of NOM. The effects of size-based adsorption/exclusion and pH-dependent electrostatic attraction/repulsion were investigated by using humic acid as model NOM and ibuprofen and methylene blue as model target contaminants. Adsorption and decomposition of the targets were dependent on their hydrodynamic size and ionization state. Mesoporous TiO2 suppressed physical access of large NOM onto its surface while reaction pH influenced the surface charge of TiO2 and the speciation of the chemicals and thus controlled their adsorption and decomposition. The results imply that selecting a proper pH can significantly improve selective decomposition of a target onto porous TiO2 in the presence of NOM.