The security pattern of the ecosystem in Huaihe River Economic Belt plays a vital role in maintaining the healthy and stable structure of the ecosystem and the green development of the ecological environment in the central and eastern regions of China. This study takes Anhui section of Huaihe River Economic Belt as the case studies, and then the Pressure-State-Response (PSR) theory was used to construct the ecosystem security evaluation index system. In addition, cloud matter element as well as resistance diagnosis model was adopted to dynamically evaluate the spatio-temporal evolution pattern. The final stage was to diagnose main obstacle factors of ecosystem security in Anhui section of Huaihe River Economic Belt from 2010 to 2018. The results indicate that: (1) Overall, the ecosystem security level of Anhui section of the Huaihe River Economic belt has undergone the evolution trend of “descending - ascending - descending - ascending”, and the overall change shows the curve of “W” shape. (2) From the perspective of spatial evolution, the ecosystem security level of southern cities is higher than that of northern cities. (3) The main obstacle factors are urban population density, the proportion of energy conservation and environmental protection expenditure in fiscal expenditure, per capita urban road area, and industrial wastewater discharge, etc. Therefore, according to the regional development differentiation strategy, it is necessary to actively advocate the development mechanism of banning new construction, closing pollution sources, and optimizing structure as well as building new green, so as to further promote the safe and healthy operation of the ecosystem in Anhui section of the Huaihe River Economic Belt.