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In this study, the relationship between land use and cover change (LUCC) and variation of groundwater level and quality in the Sangong Oasis Region was investigated using a spatial geostatistical approach. Specifically, interactions among groundwater, surface water, and LUCC were analyzed through the utilization of geographical information system (GIS), remote sensing (RS)Imagery processing, and geostatistics. Study outputs indicated that recharging into the groundwater did not change significantly during the period from 1978 to 1998. However, both LUCC and groundwater level changed substantially in the Sangong Oasis Region, and their variations were closely correlated to each other spatially and temporally over the past two decades. It confirmed that urbanization process and increased industrial activities were the direct reasons of groundwater table descending and the deterioration of water quality. The results of this research provided a scientific basis for understanding sustainability-related problems and solution options in the oasis areas of western China.