The nanomechanical behaviors of (110) and (111) CdZnTe crystals were investigated by nanoindentation. It was found that the indenter tip was adhered by the removed materials in scanning testing area although the scanning force on the tested surface was very small (1000 nN), which would affect the testing result of nanoindentation, so the indenter was clean before nanoindentation test. The experimemtal results showed that the hardness and Young’s modulus decreased with the increase of indentation loads on the same plane. Because of the anisot-ropy of the CdZnTe crystal, the average hardness of (110) plane is 35% lower than that of (l 11 ) plane, and there are about 30% difference of the hardness along different crystallographic directions on the same plane. The hardness in 0° and 120° testing directions was the same due to the threefold symmetry of a Berkovich indenter. And the anisotropy affected the surface quality during machining of CdZnTe crystal.