Abstract Quantifying the uncertainty of non-stationary flood frequency analysis is very crucial and beneficial for planning and design of water engineering projects, which is fundamentally challenging especially in the presence of high climate variability and reservoir regulation. This study proposed an integrated approach that combined the Generalized Additive Model for Location, Scale and Shape parameters (GAMLSS) method, the Copula function and the Bayesian Uncertainty Processor (BUP) technique to make reliable probabilistic interval estimations of design floods. The reliability and applicability of the proposed approach were assessed by flood datasets collected from two hydrological monitoring stations located in the Hanjiang River of China. The precipitation and the reservoir index were selected as the explanatory variables for modeling the time-varying parameters of marginal and joint distributions using long-term (1954–2018) observed datasets. First, the GAMLSS method was employed to model and fit the time-varying characteristics of parameters in marginal and joint distributions. Second, the Copula function was employed to execute the point estimations of non-stationary design floods. Finally, the BUP technique was employed to perform the interval estimations of design floods based on the point estimations obtained from the Copula function. The results demonstrated that the proposed approach can provide reliable probabilistic interval estimations of design floods meanwhile reducing the uncertainty of non-stationary flood frequency analysis. Consequently, the integrated approach is a promising way to offer an indication on how design values can be estimated in a high-dimensional problem.