In this study, nanoindentation and nanoscratching were employed to research on the mechanical anisotropy of CdZnTe (110) and (111) planes, and their effects on the grinding of CdZnTe wafers were studied. The results suggest that the primary slip system is responsible for the anisotropy of hardness and frictional coefficient. It is easy to slip along 110 directions on (110) plane and 112 directions on (111) plane during scratching, hence the frictional coefficient is the lowest compared to that of other directions, and high surface quality could be obtained during grinding along these directions. The problem of embedded abrasives, which is due to the soft nature of CdZnTe crystal, could be solved when using the grinding process instead of the lapping process.