The hydrological regimes of downstream reservoirs have been significantly altered due to the operation and regulation of upstream cascade reservoirs. The original design flood quantiles, namely "design flood in construction period", do not consider anthropogenic impacts in reservoir operation period, and have led to enormous conflicts between flood control and conservation. In this study, the "design flood and flood limited water level in operation period" are defined for practical application. We establish a general framework to measure the spatiotemporal pattern of streamflow and to estimate design floods of cascade reservoirs in operation period.The multivariate t-copula and a genetic algorithm strategy are proposed to solve the curse of dimensionality encountered in the derivation of most likely regional composition. The Jinsha River and Yalong River cascade reservoir system in China, which consists of 13 large reservoirs with the total storage capacity of 74.06 billion m 3 and hydropower capacity of 71.47GW, is selected as a case study. Results indicate that: (1) The curse of dimensionality can be well addressed by applying multivariate t-copula to build high dimensional joint distribution and using the genetic algorithm to achieve the most likely regional composition. (2) Compared with the design floods in