River cascade development affects the hydrological and habitat characteristics of the region and disrupts the dynamic balance of stable river ecosystems. The most profound impact of river cascade development is on the resident fish species. River ecosystem restoration for maximum river habitat improvement is generally based on water security and environment improvement and effectively embodies the nature-based solutions (NbS) concept of naturalized restoration. Yuanjiang (Y.J.) River is an international river in southwest China seriously affected by cascade development. By determining the response of the river ecosystem and using the key performance indicator method, Yuanjiang carp (Cyprinus carpio rubrofuscus) and red giant catfish (Bagarius rutilus) were identified as the key species in the main stream of the Y.J. River., and the ecological effects of river cascade development on them were studied by applying two-dimensional hydrodynamic physical habitat simulation and multi-objective ecological scheduling models. Based on the calculation results for ecological operation optimization of cascade reservoirs, an improved progressive optimality algorithm was used to calculate the ecological flows required to maintain the stability of the river ecosystem. With the increasing extent of cascade development in the river, important indicators, such as the intra-annual, extreme, high, and low flows have changed significantly, and the hydrological characteristics of the main stream have changed rapidly and comprehensively. Habitat suitability curves were used to determine the appropriate water depth and delineate the weighted usable area required for the spawning, nursing, and growing periods of the key fish species. The suitable ecological flows required for the three life-cycle stages of the C. carpio rubrofuscus accounted for 34, 45, and 62 %, respectively, of the multi-year mean natural water inflow at the Qiaotou (Q.T.) cascade, whereas those required for the three respective periods of B. rutilus accounted for 47, 98, and 27 %, respectively, of the multi-year mean natural water inflow at the Madushan (M.D·S.) cascade. Considering the physiological lifecycle demands of the indicator/key fish species and the upper limit of water resources development and utilization in the key river section, the ecological flow precipitation frequency in the Q.T.-Luodie (Q.T.-L.D.) and M.D·S.-Xinjie (M.D·S.-X.J.) sections (currently at 25, 50, and 75 %, respectively) can be increased to 100 % under optimal operating conditions (cascade hydropower station optimal operation). After implementing the multi-objective ecological operation at the Y.J. River main-stream cascade reservoirs, the suitable habitat area for C. carpio rubrofuscus and B. rutilus increased significantly (>10 % and 15 %, respectively). In general, the NbS-based ecological flow calculation method for cascade-developed rivers has a wide range of applications, which can be useful for the eco-environment restoration of rivers and improving the living habitats of waterway organisms.