In order to explore the impact of Kaidu River inflow, land and water resources exploitation, and hydraulic engineering regulation on the changes of water and salt balance in Bosten Lake under changing environments, the water-salt budget model of Bosten Lake was constructed according to the hydraulic connections and water-salt transport process between rivers, lakes and water conservancy projects. Based on the systematic observation data of meteorology, hydrology, salinity and human activities from 1955 to 2020, the annual, phased and multi-year water-salt budget were analyzed. The results show that under the influence of Kaidu River inflow and human activities, the water and salinity of Bosten Lake from 1955 to 2020 showed the variation characteristics of four phases, and the water and salinity variation rate has increased since 1987. In terms of inflow, the water diversion from the Yanqi Basin and Kongqi River was relatively stable, and Kaidu River inflow accounted for 81.89% of the total inflow of the lake, which played a leading role in the variation of water level of Bosten Lake for the last 70 years. The salt drainage of farmland accounted for 37.24% of the total salt intake of the lake during 1955-1987, and that during 1972-1986 accounted for nearly 50%. Salt drainage of farmland was mainly responsible for the rapid increase in lake salinity. After the operation of Bosten Lake water pumping station in 1983, the salinity of the lake water decreased as a whole, which dropped below 1g/L in 2020. Besides the strict control of water resources in the Kaidu-Kongqi River Basin in the new era, it is suggested that the joint operation of the pumping station, Baolang Sumu diversion brake, and Dawuti brake should be fully leveraged in the future, thereby maintaining the salinity of Bosten Lake below 1g/L. The research findings can provide a foundation for the sustainable utilization and management of Bosten Lake.