The work aims to effectively reduce the plate-making quality problems caused by the thermal expansion of the ball-screw drive system of the CTP plate-making machine. By taking the thermal error experiment of the CTP ball-screw drive system, the relationship between the expansion amount, the screw temperature and the screw position was analyzed and the mathematical model of compensation was established. Proved by experiment, the deviation between the calculated values and actual measured values of the obtained model was kept within the range of [0.0320 mm, 0.0406 mm]. Therefore, the operator could use the CTP driver software to apply the calculation results of the model to optimize the thermal error of the CTP plate-making machine, and compensate the thermal error of the scanning head, and then improve the quality of the CTP plate-making. The thermal error compensation of the CTP plate-making machine can effectively reduce the change of the scanning position of the scanning laser head caused by the thermal expansion of the ball-screw system, the offset, deformation, misregistration of the plate content, etc., so as to improve the printing quality.