This study uses the wind–vehicle–bridge coupling vibration analysis method to investigate the bridge stiffness problem of a large-span cable-stayed-suspension cooperative system. On the basis of the particle-damping-spring vehicle model, the TMeasy surface contact tire model is introduced, and a set of universal wind–vehicle–bridge coupling analysis algorithm is built in the framework of the whole process iterative method. Based on the Latin supercube sampling principle, random traffic flow is generated and loaded onto bridge structures with different stiffness conditions to analyze the driving comfort and safety under each stiffness condition. Combining the specification requirements, engineering experience, and research results, the vertical stiffness limit applicable to the bridge of the highway cable-stayed-suspension collaborative system is proposed. Existing engineering experience shows that the vertical deflection-to-span ratio of a cable-stayed bridge under live load is distributed between 1/400 and 1/1600, and the vertical deflection span ratio under the action of lane load is recommended based on numerical analysis.