The design and full closed-loop controls of micro/nano positioning system are presented in this paper. The micro/nano positioning system mainly consists of a 3-DOF compliant mechanism, a micro-vision system and three piezoelectric actuators. In order to compensate for nonlinear hysteresis in the piezoelectric actuators, an adaptive controller using direct inverse modeling approach based on a modified Prandtl–Ishlinskii model is presented. Instead of using traditional displacement sensors, a micro-vision system (MVS) is used to obtain feedback signals online. Based on the micro-vision system, a full closed-loop tracking control is developed to enhance the positioning accuracy of micro/nano positioning system. Taking into account the coupling motions, another full closed-loop tracking control with a decoupling feedforward controller is also proposed. Experimental results demonstrate that the full closed-loop controls can improve the positioning accuracy when compared with an open-loop control. Furthermore, the decoupling feedforward controller can improve the tracking performance of full closed-loop tracking control as well.