A TiO2-based photocatalytic oxidation study of volatile organic compounds (VOCs: benzene, toluene, ethylbenzene, and xylenes) requiring close monitoring of the catalyst coating, its deactivation, and regeneration was undertaken. For all experiments, the effectiveness of sol–gel coating of nanosized TiO2 particles (on a glass cylindrical reactor) in terms of the surface morphology, film thickness, and band-gap energy was ensured for obtaining a consistent reactor performance. The estimated VOC degradation rate constants (range of 1.16 ± 0.06–1.79 ± 0.05 min–1 m–2) were comparable or higher than those reported in the literature. Reduction of the degradation rates [48% (o-xylene) and 59% (toluene) over a 13 h operation period] with successive deterioration of the catalyst surface appeared to be a major challenge both for design of the reactor and for its long-term operation. A set of definite suggestions has been made for design criteria (degradation rate) and the frequency and method of catalyst regeneration for long-term field operations.