Abstract: Based on the samples of river water, groundwater, precipitation, and glacier meltwater collected from Lhasa River basin during the dry and wet seasons, the characteristics of sub-basins, such as area, topography, lithology, and glacier coverage for the sampling sites, were extracted. The Piper diagram and Gibbs diagram were used to analyze the controls of river hydro-chemical characteristics by rock chemical weathering, and methods of principal component analysis and correlation analysis were used to reveal the relationship between the main chemical components of river water and the landscape factors of sub-basins. The results show that the hydro-chemical type of river water is mostly HCO₃-Ca, which is mainly affected by the weathering of carbonate rock and the dissolution of evaporative rock. During the wet season, the hydro-chemical characteristics of the river water are also affected by precipitation and glacial meltwater. Generally, the contents of chemical compositions of the river water change with landscape characteristics. With the increase of sub-basin area and the decrease of altitude, the water-rock interaction and carbonate weathering are enhanced, while the dissolution of the evaporative rock is weakened. During the dry period and in glacierized sub-basins, the influence of evaporite on the chemical compositions of the river water is of great significance due to the large areas of sub-basins and the strong groundwater recharge. The study provides a scientific basis for revealing the controlling factors and regional patterns of the chemical characteristics of river water in cold and high-altitude areas.