With the refinement of civil aircraft technology and the enhancement of product complexity, civil aircraft design has changed from traditional text-based system engineering to model-based system engineering, the expression of the system has also transformed from text-centered to model-centered. To further improve the model quality and correctness of aircraft system modeling, this paper explores the applicability of model-driven and verification-oriented system engineering methods in the field of civil aircraft design, and establishes the system engineering practice framework of civil aircraft design, which can ensure the rapid design and efficient delivery of civil aircraft. Firstly, starting from the Harmony SE modeling method, the workflow and modeling ideas of system are introduced; then the noticeable problems in the practice of civil aircraft system engineering are analyzed, and the system engineering practice of civil aircraft design is established with the support of the applicability of the Harmony SE method; finally, the fuel tank pressurization component is taken as the research object of the practice system in component-level. The results show that the system engineering practice framework of civil aircraft design and method proposed in this paper can correctly and reasonably allocate design requirements and establish a complete system model, which is helpful to improve the efficiency and accuracy of civil aircraft design at this stage.