The climate is becoming warmer and more humid in the inland area of northwestern China. In addition, human activities have changed the underlying surface of the river basin, and the instability of the runoff changes has intensified. As a component of river runoff, the base flow reflects the impacts of climate change and human activities. Therefore, it is necessary to carry out research on the change in the base flow and its influencing factors in the context of climate change and human activities. In this study, a base flow method suitable for the inland rivers in northwestern China was assessed, and the variation rules and influencing factors of the base flow were analyzed. The results reveal that since the 1980s, the base flow of the Hexi inland rivers has exhibited an increasing trend, and the growth rate has exhibited the following order: western > central > eastern. The Base Flow Index (the proportion of the base flow to the total runoff in a period) values are in the range of 0.45–0.65. Overall, the change in the base flow of the Hexi inland rivers is the result of the coupling of climate factors and land-use change. The influence of land-use change on the base flow of the Hexi inland rivers gradually weakens from east to west, except for the Xiying River, while the influence of climate change gradually increases. The contribution rates of land-use change to the base flow in the eastern, central, and western regions were 75%, 55%, and 27%. Temperature and precipitation are the main climate factors affecting the change in the base flow in the western and central regions, respectively.

Rapid economic and societal development increases resource consumption. Understanding how to balance the discrepancy between economic and social water use and ecological water use is an urgent problem to be solved, especially in arid areas. The Heihe River is the second-largest inland river in China, and this problem is notable. To ensure the downstream ecological water use, the “Water Distribution Plan for the Mainstream of the Heihe River” (97 Water Diversion Scheme) controls the discharge of Yingluo Gorge and Zhengyi Gorge, while the “Opinions of applying the strictest water resources control system” (Three Red Lines) restricts the water use. With the development of the economy and agriculture in the midstream, Zhengyi Gorge’s discharge cannot reach the Heihe River’s ecological water downstream. This paper is under the constraints of the “97 Water Diversion Scheme” of Heihe River and the “Three Red Lines” of the total water use control index for Zhangye County. We constructed a water resource allocation model for the midstream of Heihe River to reasonably allocate water resources in the Heihe River’s midstream and downstream. This model is divided into three parts: Establish the mathematical equation, simulate the water consumption under the different inflow conditions, and ensure each water user’s demand. The result showed that if we fail to confine total water consumption in the midstream, through the reasonable allocation of water resources, the real water use and water consumption of the middle Heihe River will be greater than the “97 Water Diversion Scheme” and the “Three Red Lines.” If we confine water consumption, they will be within the “97 Water Diversion Scheme” and the “Three Red Lines,” at the same time, they can reach the downstream of the Heihe River’s ecological water. Besides, under the premise of satisfying the economic water and ecological water downstream of the Heihe River, returning farmland to wasteland and strengthening water-saving measures will improve water efficiency and be more conducive to allocating water resources.