According to new practices of flood control and river survey of the Yangtze River during 2016-2019, changes and new situations of river floods and river regime, as well as previous researches and achievements, the author presents ten key issues on flood control and river regulation for the middle and lower Yangtze River after the 2016-type flood. Such key issues include: variation of river discharge and sediment load; change of river regime; change of hydrological rhythm; fluvial processes; change of river storage; relationship of river and lakes; relationship between stage and discharge; adjustment of flood control strategy; technology of river regulation; and research on river management and protection. The ten issues are sorted and decomposed into a four-step framework, namely, Cause-Effect-Impact-Response. The four-step framework contains two sets of relations (a z-shaped driving mode relation and a square-shaped intercorrelated relation). The research finding enhances understanding on the impacts of the Three Gorges Project on river flood and river regime in the middle and lower Yangtze River, and also helps strengthen the hierarchical and systematic understanding on issues of flood control and river regulation.