Abstract: Field investigations and studies indicate that climatic variation and human activities have important impacts on groundwater circulation and regeneration-evolution in the Heihe River drainage area of the northwest endorheic drainage region. Shallow groundwater in the plain is mainly recharged by modern water. 35% of it is recharged by surface runoff transformed from bedrock fissure water of the Qilian Mountains and the rest is recharged by infiltration of precipitation and melt water in the piedmont Gobi belt, both of which have a strong regeneration ability. Confined groundwater mainly originates by recharge of regional meteoric water and river water in the geological history, which has relation with modern water circulation. The influence of human activities in the middle reaches of the river is an important factor responsible for the weakening of the groundwater recharge ability, sustained lowering of groundwater level and eco-environmental degradation in the lower reaches. Therefore, the scientific regulation of the human activities in the middle reaches is the key to realizing sustainable utilization of groundwater resources in the Heihe River drainage area and effective protection of the ecological environment in the lower reaches.