Titanium dioxide (TiO2) nanoparticles have been extensively studied for catalyzing the photo-degradation of organic pollutants, the photocatalyst being nonselective to the substrate. We, however, found that TiO2 nanoparticles prepared via the sol-gel and hydrothermal synthetic routes each possess a definite specificity to the charge of the substrate for photodegradation. The nanoparticles were characterized by SEM, FTIR, XRD, TGA, and UV-visible spectra, and the photocatalytic degradation under UV-B (285 nm) irradiation of two model compounds, anionic methyl Orange (MO) and cationic methylene blue (MB) was monitored by a UV-visible spectrophotometer. Untreated sol-gel TiO2 nanoparticles (Tsg) preferentially degraded MO over MB (90% versus 40% in two hours), while after calcination at 400 °C for two hours (Tsgc) they showed reversed specificity (50% MO versus 90% MB in one hour). The as-prepared hydrothermal TiO2 nanoparticles (Tht) behaved in the opposite sense of Tsg (41% MO versus 91% MB degraded in one and a half hours); calcination at 400 °C (Thtc) did not reverse the trend but enhanced the efficiency of degradation. The study indicates that TiO2 nanoparticles can be made to degrade a specific class of organic pollutants from an effluent facilitating the recycling of a specific class of pollutants for cost-effective effluent management.