Abstract: The accuracy of thickness measurement is not high or the measurement method is too complicated at present. It is of great significance to design a set of high-precision thickness measurement device with simple operation, high efficiency, non-destructive measurement and wide application range. In this paper, a high-precision thickness measurement system is developed by using ²⁴¹Am radioactive source and cadmium zinc telluride (CZT) detector, and a measurement condition compensation method is proposed to achieve non-destructive and high-precision online measurement of samples. The Geant4 program package is used to simulate the design of a high-precision thickness measurement system, and the influence of key parameters such as the size of the collimation hole, the relative position of the source and the detector, and the thickness of the shielding layer are determined. Use the built high-precision thickness measurement system to measure samples such as paper, circular truncated cone sample, ceramics and high-speed steel. The experimental results show that the system can achieve high-efficiency, online thickness measurement when the thickness accuracy is on the order of 100 microns; when the measurement accuracy is required to increase, high-precision measurement can be achieved by extending the measurement time and using the measurement condition compensation method., for example, for a material with a thickness of 1 mm, the measurement accuracy can reach 1 μm; at the same time, the system works stably for a long time, and the relative standard deviation within 24 h is about 0.057%.