An optimal topology design method for multiple inputs and multiple outputs compliant micro-manipulation system is presented. Firstly, the topology design problem is posed in terms of a multiple inputs load and several specified output deflections. The compliance and stiffness of the system are expressed by the mutual potential energy and strain energy, respectively, which can be controlled by a multi-critaria objective function. Secondly, based on the optimality criteria method, a model solution algorithm is presented. Finally, a numerical example is presented to show the validity oftbe presented technique. The optimal topology ofa 4 inputs and 4 outputs compliant mechanism is obtained by using the method, and the corresponding micro-positioning stage system is further designed.