The vibration response of the flexible beam under the coupled multi-moving masses with variable speeds is studied. Based on the vibration theory of the flexible beam, the vibration model of the multi-moving masses-flexible beam system is established. The interaction among the moving masses and the coupling effect between the motions of moving masses and the vibration of the flexilbe beam are considered in this model. The numerical simulation is conducted by solution method of time-variant mechanical system. Results show that the vibration response of the flexible beam is different under different forms of motion among the moving masses, and the coupling effect among moving masses enhance the vibration response of the flexible beam.