The piezoelectric actuator demonstrates superior characteristics of high displacement resolution, miniature size, high-frequency response, strong power, no generate heat etc, So it is used in nano systems widely. But its inherent hysteresis, creep and non-linearity affect positioning accuracy seriously. In this paper, through the investigative experiment of a large travel piezoelectric actuator worktable’s creep characteristics, creep characteristic curve and the rules of the piezoelectric actuator creep were found. Based on the rules of the piezoelectric actuator creep characteristics, the piezoelectric actuator creep resistance driving method of two-level reversely applied voltage could remarkably reduce the creep error of system, namely, applying stepped voltage reversely according to two stages. The experiments show that the creep error of the system has been reduced from 3.80% to 0.26%, the period of creep tends to be stable, and also has been shortened within 10 seconds. This driving method make the quick and precise piezoelectric actuator positioning control with large displacement become possible. It also provides further scientific method to amend and reduce the creep effect of piezoelectric actuator, and improves the positioning accuracy of the system.