In this article, a novel XYZ nanopositioning stage with hybrid structure configuration is developed to obtain translation motions along the x, y and z directions with high working bandwidth. A novel Z-shaped flexural guidance unit with self-amplification is adopted to generate motions along the x and the z directions by means of differential motion principle. Simultaneously, a right circular-based guidance unit is embedded to generate the motion along the y direction independently. The corresponding working principles in the three directions are detailed in this article. In addition, the statics and dynamics performances of the developed mechanism are investigated by experiments. The workspace of the XYZ stage can reach up to 20.8 µm × 12.2 µm × 23.1 µm with a practical working bandwidth larger than 250 Hz.