Abstract: In this study, Tonle Sap Lake Basin was selected as the study area. Based on the Landsat TM image data in 6 years (1988, 1991, 1995, 2005, 2007, 2009), spatial-temporal variation characteristics of the wetland were studied by means of tasseled cap, spatial autocorrelation analysis and transition matrix. The results showed that the global Moran's I of the humidity index of the wetland was between 0.789−0.831 (P<0.01), showing a significant positive spatial autocorrelation, but the degree of spatial agglomeration showed a downward trend with a rate of 0.52% every year. In the six periods, the humidity index of the wetland showed a downward trend with a rate of 0.02% every year, and the humidity index in 2007 was the lowest. The humidity index showed the distribution pattern of 'high-low-high' from inside to outside. Vegetation wetlands decreased from 18 580.21 km² in 1988 to 18 435.24 km² in 2009, and non-vegetation wetlands decreased from 3 739.64 km² in 1988 to 3 510.50 km² in 2009. Large-scale deforestation in the Tonle Sap Lake Basin had an important impact on the reduction of wetland area in 1998−2009. This study can provide a certain reference value for the sustainable development of wetland resources in the Tonle Sap Lake Basin.