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High-performance connection frames are of great significance for ultra-high acceleration and ultra-precision positioning in macro-micro motion platforms. This paper first takes the connection frame as a research object,builds a finite element model (FEM) of the natural frequency of the frame, and then verifies the correctness of this model. The frequency sensitivity method is then used to perturb the structural parameters of the FEM of the connection frame, and the sensitivities of the first-order natural frequency and mass of the corresponding structural parameters are obtained by calculation and analysis. The design variables are also determined. The naturalfrequency is used as the optimization objective, and the design parameters andmass of the connection frame are constrained. The structural parameters of the connecting frame are obtained through optimization, and the model is built and verified by experiments. The results show that the first-order natural frequency of the connecting frame is effectively improved by the frequency sensitivity method, avoids resonance between the connecting frame and the voice coil motor, and realizes the lightweight design of the connection frame. This research provides a reliable basis for the stable operation and ultra-precision positioning of ultra-high acceleration macro-motion platforms.