Abstract: Carrying out water resource vulnerability assessment is an effective way to strengthen water resource management. Aiming at the problem that the linear expression of the connection number in the set pair analysis cannot accurately reflect the ambiguity and randomness existing in the water resources system, the cloud model is introduced to improve the calculation of the connection number in the set pair analysis. The analytic hierarchy process and entropy weight method are combined to calculate the combined weights of the evaluation indexes through the principle of maximizing variance, and the set pair cloud model of fusion weights is established. The model is applied in the water resource vulnerability assessment in the prefecture-level cities of Henan Province from 2010 to 2019. Moreover, the five-element subtraction set pair potential is introduced to analyze the development trend of water resource vulnerability in prefecture-level cities. The results show that there are three levels of water resources in Henan Province: mild vulnerability, moderate vulnerability and severe vulnerability.The distribution shows that the overall water vulnerability of the cities in the south and the west are lower, and the cities in the north and the middle are more vulnerable, mainly due to the lack of natural endowments and the high degree of development and utilization of water resources. The system situation of Xinyang, Sanmenxia and Zhumadian are in the trend of equilibrium potential or partial identical potential in most years, with a better state of water resources vulnerability than the remaining cities and a healthy development situation. In Zhengzhou, Jiaozuo, Kaifeng and other cities, the overall situation of system are in the trend of inverse potential or partial inverse potential in all years, so the development situation is severe, which belongs to the areas where water resources vulnerability need to focus on regulation.The implementation of the strictest water resource management system in Henan Province and the supply of water from the South-to-North Water Diversion Central Project have eased the pressure of water shortage, and the vulnerability of water resources has shown a downward trend since 2014, which is in line with the actual situation of Henan Province. The research findings can provide a decision-making basis for the rational development and utilization of water resources and the coordinated development of water resources, socio-economic and ecological environment in Henan Province.