In order to explore the impact of land use change on lake water quality in Tonle Sap Lake Basin, the methods of GIS spatial analysis, Theil-Sen Median trend analysis, Mann-Kendall test and correlation analysis were used to systematically investigate the spatio-temporal variation characteristics and the correlation of land use and lake water quality in recent 20 years based on MODIS land cover products (MCD12Q1), lake turbidity and nutrient state index data. The results showed that land use in the Tonle Sap Lake Basin was mainly characterized by a significant decrease in forest land (P < 0.01) and a significant increase in grassland and cropland (P < 0.01), with the average annual change rates reaching -1.13%, 0.8% and 0.35% of the total basin area, respectively. Meanwhile, the lake turbidity and nutrient status index showed an upward trend, but did not pass the significance test. During the study period, lake turbidity was strongly negatively correlated with forest land (r = -0.65), strongly positively correlated with grassland, cropland, and construction land, with correlation coefficients of 0.61, 0.74, and 0.72, respectively. It was also weakly positively correlated with wetland (r = 0.35). However, lake trophic state index was only weakly negatively correlated with wetland (r=-0.31). It is concluded that the above conclusions provide scientific references for understanding the driving factors of water quality changes in Tonle Sap Lake and basin management.