Abstract: The joint operation of upstream reservoirs has changed the natural inflow and sedimentation of the cascade reservoirs in the lower Jinsha River. The original design floods and flood control water levels (FCWL) cannot meet the demands of flood-drought prevention and efficient utilization of water resources in the new era. To quantify the impact of upstream reservoir regulation, the most likely flood regional composition (MLFRC) method and the most unfavorable flood regional composition (MUFRC) method are modified based on vine copula. The design floods of cascade reservoirs in the lower Jinsha River are estimated and compared with the non-stational flood frequency analysis (NFFA) method, and FCWLs and hydropower generation benefit are also reevaluated. The results show that: (1) The regulation of upstream cascade reservoirs has significantly reduced the design floods, and the 1000-year design peak discharge, 3d, 7d, 15d, and 30d flood volumes in the operation period of Xiangjiaba reservoir are reduced by about 39%, 36.6%, 35.1%, 26.0%, and 15.7% compared to natural design values. (2) Maintaining the original flood control standards unchanged, the FCWLs of Wudongde, Baihetan, Xiluodu, and Xiangjiaba reservoirs can be raised to 958.56 m, 794.67 m, 568.75 m, and 373.42 m, with an average additional power generation of 2.43 billion kW·h from June to September. (3) The results of the MLFRC and MUFRC have no significant difference from that of NFFA, but can reflect the flood control and scheduling process of upstream reservoirs in detail. The research can provide theoretical and technique support for the operation of cascade reservoirs in the lower Jinsha River.