A compliant piezo-driven puncture mechanism was proposed. Firstly, to amplify the output displacement of the piezoelectric actuator, a bridge-type displacement amplification mechanism was designed based on the principle of compliant mechanism. Considering the purpose of improving the lateral stiffness, the overall structure was then designed. By combining the pseudo-rigid-body method and the Euler-Bernoulli flexible beam theory, the static model of the proposed mechanism was established. After that, the dynamic equation was also obtained by the Lagrange method and the natural frequencies were eventually calculated. Through the differential evaluation algorithm, the geometric parameters of the flexible hinges were optimized and compared with the results obtained by the finite-element analysis method. Finally, physical experiments were conducted and validated that the proposed compliant puncture mechanism can achieve the displacement amplification ratio of 9.8, leading to a stroke of 180μm. Besides, under the action of the disturbance observer-based PID control, the proposed mechanism guaranteed good performance with the root mean square error and maximum error of 0.071μm and 0.128μm.