The ecological security of rivers is not only closely related to the physical, chemical and biological integrity of the river itself, but also affected by the natural, economic and social conditions of the regions through which it flows. Based on the "driving force-pressur-state-function-response" (DPSFR) framework and matter-element extension model, a river ecological security evaluation system was constructed. Taking Hongru River as an example, it was divided into 10 evaluation units according to the spatial differences such as physical geography and water conservancy projects, and the river ecological security evaluation and spatial differentiation characteristics research were carried out. The results show that the ecological safety level of the Hongru River in 2017 was in a critical safety state, and there was a tendency to develop to an unsafe level. Its spatial differentiation characteristics were that the upstream was better than the downstream, and the tributaries were better than the mainstream, especially in the functional and response layers. Among the indicators, total phosphorus, per capita comprehensive water consumption, river longitudinal connectivity, and water quality assessment cross-section compliance rate are the main factors affecting the spatial distribution of ecological security differences in Hongru River. The response is a criterion layer that is significantly related to the spatial differentiation of the ecological security of the Hongru River.