A cutterhead endures complex random loads when the TBM tunnels, which leads to structure excessive vibration, due to the extreme working conditions. So anti-vibration design is key in the cutterhead system design. In this study we established a virtual prototype of TBM mainframe system, comprehensively considering the spatial multi-point random excitations, split cutterhead structure and multidirectional support stiffness of the main bearing, etc., based on multi-body system dynamics and virtual prototype technology. For verifying the virtual prototype model, a TBM cutterhead vibration field detection system was constructed, to test the cutterhead accelerations and compare the simulation and measured results. The results show that the acceleration change rule by the two approaches is similar, and the maximum relative error is 55 %, keeping on the same order of magnitude, which illustrates the established model has certain reliability. Accordingly, an orthogonal test scheme for cutterhead radial vibration analysis was designed, to analyze the influence of different parameters on cutterhead vibration, based on the virtual prototype model. As indicated in the analysis, the parameter of cutter force had the greatest influence on cutterhead vibration, and then the pinion support stiffness and cutterhead rotating speed. Last, the cutterhead vibration optimal schemes in different directions were confirmed. The research results and methods can provide reference for TBM system parameters matching.