The state of ecosystem services is closely related to whether the ecosystem is safe or not. The normal play of ecosystem services is the premise of realizing ecological security. Recently, the expansion speed of desert oasis in Northwest China has accelerated which has changed the supply and transmission of ecosystem services, and further affected the regional ecological security. Taking the middle reaches of the Heihe River in typical desert oasis region as an example, based on Pressure-State-Response model, coupled with the ecosystem service theory, the ecological security evaluation index system of the middle reaches of the Heihe River was constructed, and the evolution trend of ecological security in the middle reaches of the Heihe River from 2001 to 2015 was evaluated. The results showed that the ecosystem in the middle reaches of the Heihe River was facing increasing pressure of resource consumption and environmental pollution, and the pressure index decreased accordingly. As vegetation degradation and fragmentation increased in some areas, the state index decreased slightly. After the implementation of water-saving irrigation, industrial transfer, wetland protection and other positive measures, the response index increased significantly. Overall, from 2001 to 2015, the ecological security level in the middle reaches of the Heihe River showed a fluctuating growth trend, the ecological security index increased from 0.3748 to 0.5888, and the ecological security level reached the state of "critical safe" from "less safe". Among them, water resources related factors such as area of efficient water-saving irrigation, ecological water consumption and groundwater development rate were the main factors affecting the ecological security level of oasis. Based on the above research, this paper puts forward relevant countermeasures and suggestions to improve the ecological security level, such as adhering to the priority of ecological protection, adjusting planting and industrial structure, developing efficient water-saving irrigation technology and improving public awareness of ecological protection, in order to provide support for promoting the sustainable development of regional ecological economy.