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Identifying the primary causes and examining the processes and trends of land use change are crucial for land use planning, utilization of regional resources and environment management. Combining the ecological quantity analysis with GIS technology, based on the land use data and remote sense images, the changes of land use and land cover and the driving force were analyzed in the mainstream of the Tarim River from 1973 to 2005. The results showed that the areas of cropland and built-up land increased obviously, grassland, forest and wetland decreased and unused land increased first and then decreased. The major patterns of land use change were from grassland (major source), woodland, unused land and wetland to cropland, from a great lot of cropland to built-up land, as well as from grassland (occupying 30 %), woodland and wetland to unused land. Land use change underwent a process of obvious change–slow change–obvious change–tremendous change in the period of 1973–2005. The influence of natural factors including elevation, slope, soil types, distance from river course and climate change on land use and land cover change was limited. Population growth, economic development and industry policy were the dominant driving force for land use and land cover change in the mainstream of the Tarim River. The sustainable use of land resources is significant to keep economic development and environmental protection in arid inland river basin.