To master the variation characteristics of water quality in Tanjiang River(TJR), the Mann-Kendall test and water quality comprehensive pollution index were adopted to analyze the interannual variation characteristics of water quality in TJR from 2001 to 2019. The principal component analysis method was employed to identify the dominant water quality parameters influencing the water quality variation in TJR. The main driving factors influencing the water quality change were analyzed by correlation model. The results show that the water quality in the upper reaches of TJR was the best but it had a certain tendency of deterioration. The water quality in the lower reaches in TJR took second place and the tendency of deterioration was not obvious. The water quality in the middle reaches in TJR was the worst and the tendency of deterioration was the most significant. The water quality parameters dominating the water quality variation were COD and BOD₅ in the upper reaches and TN and NH₃-N in the middle reaches as well as TN, NH₃-N and TP in the lower reaches of TJR. Population and forest coverage rate were the main driving factors influencing the water quality variation in the upper reaches of TJR, while GDP and water temperature were also the driving factors influencing the water quality variation in the middle and lower reaches of TJR besides population and forest coverage rate. Additionally, the relationship between the water quality change and natural driving factors were changed due to the impact of human factors.