In this paper, a two-loop controller is proposed to suppress the hysteresis and to achieve a precise motion tracking control for a piezo-driven XY parallel micropositioning system. Specifically, an inner-loop disturbance observer (DOB) is employed to tolerate the unmodeled hysteresis which is treated as a disturbance to the nominal plant model of the system, and an outer-loop feedback controller is used to compensate for the remaining nonlinearities and uncertainties. The effectiveness of the proposed controller over the sole PID controller is demonstrated through experimental studies. Results show that the DOB-based two-loop control can reduce the hysteresis to a negligible level and lead to a motion tracking with submicron accuracy, which provides a sound base of practical control of the micropositioning system for micro/nano scale manipulation. © 2010 IEEE.