River ecosystem is one of the most important natural ecosystems. It plays a vital role in the exchange of material, energy and information. Humans have been altering natural rivers for different purposes such as navigation, irrigation, flood control, and power generation. While great social and economic benefits are achieved, these projects can cause ecological problems such as eutrophication, black and odorous water, and insufficient eco-flow. The problems of river ecosystem health as a result of human activities have drawn great attention. Questions remained unclear regarding river management. One is the method to evaluate river health condition affected by humans. The other is to minimize the adverse impact of water conservancy and hydropower projects on river ecosystem. In this study, a river health evaluation method was proposed from the perspective of ecosystem integrity, stability, and sustainability. The proposed method is based on the harmony theory, the comprehensive weight model combined with the least squares method, and the entropy coefficient method. A new framework for assessing river health was developed from the perspective of harmony and health between hydraulic engineering and the river ecosystem. As a case study, the method and framework were applied to the middle and lower reaches of the Hanjiang River, an important tributary of Yangtze River, China. The health status of the river ecosystem and crucial drivers were evaluated. The results indicated that:(1) a total of 11 indicators including sediment transport, river connectivity, eutrophication status, fish biological integrity index, etc. contributed to the index system for health assessment of the studied site; (2) the ecological environment of Hanjiang water was generally poor and change gradually along the river. River health levels were generally "healthy" in the upstream, mostly "sub-healthy" in the midstream, and "unhealthy" in the downstream. This indicates that pollution in Hanjiang River was more serious in the downstream; (3) the physical attributes of the river were altering to that of a lake due to an increasing number of cascaded dams and inter-basin water transfer projects. The speed of such a change scales with the extent of hydraulic engineering intervention. This study will serve as an important reference for basin management in Hanjiang River.