The work aims to design and implement a shaftless drive printing control system based on the sliding mode variable structure control method to solve the problem of precise synchronization control and stability in the letterpress printing machine system. Through analyzing the control principle of the traditional letterpress rotary printing system, the control model of the shaftless drive letterpress multi-group printing units system was established to ensure that the drive motors could accurately synchronize the position and speed during the printing process so as to maintain the coordination and consistency of the printing operation. A sliding-mode variable structure control algorithm strategy was proposed. A shaftless drive control simulation system with permanent magnet synchronous motors as actuators was built. A hardware system with S7-1200 as the control core was developed, and TIA portal was used to write the PLC control program. The shaftless drive control system of letterpress with sliding mode variable structure control had good accuracy and stability, and could realize shaftless drive control in the printing process stably and reliably. Taking the letterpress rotary printing press as the starting point, the sliding mode variable structure control is introduced into the shaftless drive control system of the letterpress printing press and applied to the PLC, and its discrete processing is applied to the PLC control system. It improves the efficiency of the letterpress printing, and is a useful attempt to the use of intelligent control algorithms in the printing control.