In order to solve the problem that the imaging performance of the instrument was continuously improved but the measurement method was lagging behind in the development process of X-ray three-dimensional size measuring machine, the uncertainty was studied, and an evaluation method based on voxel model was proposed. Firstly, starting from the principle of X-ray detection, the influencing factors of digital space such as original projection, three-dimensional reconstruction, surface measurement and point cloud fitting in the size calculation process of X-ray three-dimensional size measuring machine were analyzed, and the uncertainty model of voxel was established. Secondly, based on the traceability and measurement results of the center distance of the selfdeveloped ball bar, the uncertainty of each parameter of the voxel model was calculated by GUM method and Monte Carlo method, and the uncertainty of the voxel model was analyzed. Thirdly, combined with the traditional uncertainty parameters, the uncertainty of the measurement results of the spherical center distance was synthesized and expanded. Finally, the reliability and consistency of the measurement and evaluation results are verified by the application of the results of the extended uncertainty. The length measurement results of the short and long ball bar standard were (32.947 7 ± 0.002 0) mm and (52.406 5 ± 0.002 2) mm, respectively. The results showed that the evaluation method obtained by the exploration refines the error source of the measurement results of the X-ray three-dimensional size measuring machine, expanded the research direction of the size measurement method of the X-ray three-dimensional size measuring machine, and provided a measurement basis for the improvement of the data accuracy of the X-ray three-dimensional size measuring machine, which had certain scientific value.