The vibration isolating suspension of the full-float cab in commercial vehicle has been studied based on the frame flexibility. The rigid-flexible multi-body vehicle vibration simulation model including the flex frame was used in simulation with ADAMS and ANSYS software. Furthermore, the ride comfort of full-float cab in a whole commercial vehicle was studied by changing the flexibilities of frame. The results showed that the ride comfort of full-float cab depended on the natural frequency and corresponding vibration mode of the frame, the ride comfort of full-float cab would become terrible if the first natural frequency of frame was less than 10 Hz or lower. It offered a valuable method to the match of the full-float vehicle parameter and the design of frame.