In order to alleviate the contradiction between water supply and demand in the Hotan River, and to improve the water resources management of the river basin, we studied the law of the water loss, water transformation and water consumption of the basin to quantitatively ascertain the internal relationship between the water inflow from the sections and water consumption of the main stream, as well as the water consumption of each section and the water loss of the river channel. Based on the surface runoff data of each section of the main stream and tributaries of the Hotan River Basin from 2006 to 2018, the Mann-Kendall trend analysis and the principle of water balance were used to analyze the water consumption change process of each river section. The results showed that the interannual surface runoff showed an upward trend, whereas the change during the year showed a “single peak”, and the wet season accounted for 74%. The first section of Uluwati-Ka River canal consumed the most water(16.97×108 m3/a), and the Yuhe Canal Head-Aigliya consumed the least water(2.81×108 m3/a). The total water consumption was consistent with the change trend of the water inflow. The river loss is significantly positively correlated with the water consumption in each river section, among which the main stream of the Hotan River had the largest water loss. It is concluded that the downstream of Yulong Kashi River and Kara Kashi River are the focus areas of river damage prevention and control, whereas the desert section of Hotan River presents a huge challenge for the task. The study of the water consumption of the river sections under different water inflow conditions, and the difference between water consumption and river water loss can provide technical support for the allocation and planning of water resources in Hotan Basin.