Abstract: Hydrochemical characteristics play a significant role in the study on water cycle and evolution of lakes. This study analyzes the main ions and hydrogen and oxygen isotopes of water collected from lakes and other water bodies across the saline lakes in Hoh Xil region to identify their hydrochemical characteristics and formation mechanism. The results indicate that: ① The lake water are weakly alkaline and salt and belong to Cl-Na water type. The water type evolves from HCO3 type to Cl type in the direction of precipitation, glacial meltwater, groundwater, river water, and lake water, accompanied with salt content increasing. ② The hydrogen and oxygen isotope characteristics show that local meteoric precipitation supplies the water of the different water bodies, which are affected by evaporation and concentration. An observed deuterium surplus indicates that evaporation and concentration are the main factors that lead to the increased salt content in the lake water. ③ The Gibbs diagram, ion ratio, and PHREEQC reverse hydrogeochemical simulation further demonstrate that the hydrochemical formation of the lake water is mainly affected by evaporation and concentration from both qualitative and quantitative perspectives. This process is accompanied by the dissolution of rock salt, dolomite, and gypsum minerals, the precipitation of calcite minerals, and Na-Mg cation exchange. This study provides theoretical support for the hydrochemical evolution of inland lakes on the Qinghai-Tibet Plateau and a scientific basis for further research on the water and salt balance of multi-source replenishment lakes in the Hoh Xil region.