Abstract: To address the structural reliability of large-diameter high-temperature air pipelines in aero-engines under complex thermo-mechanical-fluid coupled loads, this paper proposes a systematic optimization design method.Through multiphysics coupling simulations of flow, heat transfer, and structural stress, the method reveals the failure mechanisms of the pipeline system and establishes a parameter optimization procedure aimed at improving fatigue life. Taking the environmental control system bleed air pipeline of a high-bypass turbofan engine as the research object, optimization design is carried out. Experimental validation shows that the proposed method can effectively reduce the risk of pipeline fracture, providing a theoretical basis and engineering reference for the design of large-diameter high-temperature air pipelines in aero-engines.