For the nondeterministic factors of an aeroengine blisk, including both factors with sufficient and insufficient statistical data, based on the dynamic substructural method of determinate analysis, the extremum response surface method of probabilistic analysis, and the interval method of nonprobabilistic analysis, a methodology called the probabilistic and nonprobabilistic hybrid reliability analysis based on dynamic substructural extremum response surface decoupling method (P-NP-HRA-DS-ERSDM) is proposed. The model includes random variables and interval variables to determine the interval failure probability and the interval reliability index. The extremum response surface function and its flow chart of mixed reliability analysis are given. The interval analysis is embedded in the most likely failure point in the iterative process. The probabilistic analysis and nonprobabilistic analysis are investigated alternately. Tuned and mistuned blisks are studied in a complicated environment, and the results are compared with the Monte Carlo method (MCM) and the multilevel nested algorithm (MLNA) to verify that the hybrid model can better handle reliability problems concurrently containing random variables and interval variables; meanwhile, it manifests that the computational efficiency of this method is superior and more reasonable for analysing and designing a mistuned blisk. Therefore, this methodology has very important practical significance.