The position of three-point support has an important impact on the stiffness and accuracy of the diamond lathe. To determine the position of the support, this paper commences by conducting static and dynamic analysis on the large-size platform machine tool whose base is 2340×1540 mm under the two support schemes. It determines the basic layout scheme of the support points of the machine tool under the change of gravity center. Subsequently, by combining the least squares fitting and particle swarm optimization algorithm with the optimization goal of minimum deformation of the machine tool base working surface, the position of the support points is optimized under the influence of the Change of Gravity center. The results indicate that the optimal solution of the design variable within the design interval can be obtained through limited sampling points and optimization iterations. The average and maximum deformation of the base working surface are 0.867 μm and 1.45 μm. They decreased by 11.17% and 26.02% compared with before optimization.