Abstract: To establish the optimal design method of multiple tuned mass damper （MTMD） for the footbridge considering the vertical human-structure interaction， the parameters randomness of the mass-spring-damper （MSD） pedestrian model is simulated， and the vertical dynamic response of the random crowd-footbridge-MTMD system is calculated based on the pseudo-excitation method. Then， the effect of vertical human-structure interaction on the dynamic response of the footbridge-TMD system is demonstrated. Finally， based on the H₂ performance of the acceleration transfer function and response surface methodology of the coupled system， an optimal design method of MTMD for footbridge vibration control considering vertical human-structure interaction is established. The results show that the dynamic response calculation method of the coupled system avoids a large number of nonlinear time history analyses， and the power spectrum and root mean square of the coupled system response can be obtained efficiently. The vertical human-structure interaction makes the TMD detuning effect significant， and the reduction rate of TMD with 3% mass ratio decreases by 37.19% when the crowd density increases from 0.25 person/m² to 1.25 person/m². The proposed MTMD optimization design method for footbridge has an average mitigation rate of over 70% for footbridge acceleration response.