A design method for a creep fatigue strength of a plate-fin heat exchanger belongs to the technical field of heat exchangers. Initial design for a plate-fin heat exchanger is performed according to application requirements, then stress assessment for the plate-fin heat exchanger is performed, equivalent mechanical parameters and equivalent thermal physical parameters of the core of the plate-fin heat exchanger meeting allowable stress requirements are calculated, thermal fatigue analysis for the plate-fin heat exchanger is performed based on the parameters, and then fatigue life and creep life of the plate-fin heat exchanger are calculated, realizing comprehensive design for the plate-fin heat exchanger for high temperature applications. The design method for a creep fatigue strength of a plate-fin heat exchanger resolves the issue in which high temperature strength design for a plate-fin heat exchanger cannot be performed by directly using finite element software due to a complex periodic structure, and provides a theoretical basis for high temperature design of a plate-fin heat exchanger, such that useful-life prediction for a plate-fin heat exchanger employed under an alternating load and in a high temperature environment is performed, and an effective method is provided for high temperature design of a plate-fin heat exchanger.