Abstract: In the long-term hydrological process over the last four decades, extensive exploitation of groundwater resources has resulted in such problems as continuous decline in groundwater level and dry-up of springs in some areas while groundwater levels were still stable in some other areas. How to judge whether the exploitation of groundwater resources is sustainable or not is a focused scientific issue. In this paper, the intermediate section of Heihe River Basin is selected as the study area. With the methods of MK test and continuous wavelet analysis, the characteristics of groundwater monitoring data with long-term series are analyzed and the regional groundwater regime are examined. By taking the regional hydrogeology into account, the equilibrium and un-equilibrium areas of groundwater are divided in the intermediate section of Heihe River Basin. The regulation amount of aquifers from 1990 to 2020 is estimated with the methods of Kriging interpolation. The regulation capacity of different regions is evaluated. The results show that the regime of groundwater level in the intermediate section of Heihe River Basin includes four types of long-term stable periodic regime: hydrology type, hydrology-exploitation type, exploitation type, and evaporation- exploitation type. Over-exploitation of groundwater or over-diversion of water resources in the upper reaches resulted in the long-term decline type of groundwater regime. The equilibrium areas of groundwater are dominated within the thick aquifers in the intermediate section of Heihe River Basin, mainly located in the Heihe-Liyuanhe River inclined plain, Jiuquan Basin, and erosion and deposition plains in the lower part of the middle reaches of Heihe River. The groundwater amount of 12.06×10⁸ m³ in aquifers of the equilibrium areas was pumped from 1990 to 2001 and 9.06×10⁸ m³ was stored from 2001 to 2020, indicating that the aquifers with large thickness can provide enough space for the long term regulation of groundwater resources. If the amount of groundwater pumping is controlled reasonably, the natural regulation capacity of aquifers in such areas can meet the water demands for industry, agriculture, and domestic use in the local area and for the eco-system in the downstream area. In the un-equilibrium areas such as the inclined plain of rivers to the east of Heihe River, Yanchi Basin, and the piedmont of Yumushan mountain, the pattern and intensity of groundwater exploitation is unsustainable. Even in wet seasons, the continuous decline trend of groundwater level cannot be changed. The measures such as decreasing groundwater pumping, and regulating diversion of surface water and groundwater pumping in the upstream area, should be adopted in order to prevent the dry-up of groundwater resources. The results of this study can provide references for management and sustainable exploitation of water resources in arid and inland areas of northwest China.