The combination of a photocatalytic reaction and microfluidic technology is an increasingly popular method utilized to continuously degrade wastewater. In this work, a novel photocatalytic microreactor with TiO 2 loaded on the channel center insert was designed and the photocatalytic degradation process of oxytetracycline (OTC) was investigated. Parameters such as TiO 2 loading, OTC initial concentration, light intensity, and ion (NO 3 − and SO 4 2−) concentrations were systematically investigated. The results show that the degradation efficiency of OTC was 56% under the optimal experimental conditions. Compared with the conventional miniaturized photocatalytic reactors, the reaction rate constant and space−time degradation efficiency of the plug-in three-dimensional photocatalytic microreactor proposed in this work were 1−2 orders of magnitude higher. In addition, dimensionless correlation was obtained to predict the degradation efficiency. This work provides a promising microfluidic technology for the process intensification of photocatalytic reaction and wastewater treatment.