The typical sectional static aerodynamic coefficients of Hunan Highway Flyover in the finished bridge state are simulated by using the method of combining the virtual wind tunnel technology and full-bridge structural 3D finite element analysis. The simulation of fluctuating wind field is carried out. And combined with the simulation results, the displacement and internal force response of the full-bridge structure under the buffeting action are analyzed. The study method and the relevant conclusion can be referred for the anti-wind design of long-span variable cross-section continuous girder bridges in China.