In order to solve the fatigue life calculation problem of engineering machinery complex machine-liquid structure, this paper proposed a calculation method for structure fatigue life based on mechanical and hydraulic co-simulation technology, taking the scissor mechanism of a scissor aerial work platform as the research object. A multi-body dynamics simulation model of mechanical-hydraulic combined rigid-flexible coupling of scissor mechanism was established, and the force status in the lifting process of scissor mechanism was also analyzed. The ultimate working status was determined at the lifting stage of 79.2 s, while the load spectrum at each key hinge point was extracted. Under the same working status of simulation, the test experiments of oil cylinder pressure and structural stress were carried out. The experimental results verified the correctness of the dynamics simulation. Then, according to the load spectrum of the hinge point and the ultimate working status confirmed by co-simulation, the static analysis of scissors arms under the ultimate working status and unit loading action was carried out to obtain the static stress distribution of scissors arms structure. Eventually, by using the hinge point load spectrum and the static stress distribution, the fatigue damage and fatigue life of scissor arms were obtained. The results confirmed that the most hazardous part of scissors arms fatigue was the connecting position of each part of scissors arms, which provided a basis for subsequent fatigue life optimization.