Estuarine waters of variable compositions are sinks for many micropollutants. The varying water properties can impact the photodegradation of organic pollutants. In this study, the combined effects of dissolved organic matter (DOM), pH, ionic strength, and halides on the photodegradation of the model organic pollutant oxytetracycline (OTC) were investigated. Suwannee River natural organic matter (SRNOM) was used as a representative DOM. The results showed that the observed photolysis rate constant (kobs) of OTC increased rapidly upon increase of pH. SRNOM induced a 11.0-17.9% decrease of the kobs for OTC. In the presence of SRNOM, the ionic strength and specific halide effects promote OTC photodegradation with a 39.2-84.2% and 7.1-28.8% increase of the kobs, respectively. The effects of SRNOM, ionic strength and halides on OTC photodegradation are pH-dependent. Direct photolysis half-lives (t1/2) of OTC were estimated in view of the more important role of direct photolysis compared to indirect photolysis. The estimated t1/2 values decreased from 187.4-206.6 d to 34.4-36.6 d as the pH increases in the Yellow River estuarine region. The results of this research demonstrate that the photodegradation rate of OTC increases rapidly in the gradient from river water to marine water in estuarine regions.