CdZnTe is the most suitable epitaxial substrate material of HgCdTe infrared detectors, because its lattice constant is able to achieve full match with HgCdTe’s lattice constant. It is always needed to etch CdZnTe substrate during the process of device separation or when we want to fabricate micro optical device on CdZnTe substrate. This paper adopts the more advanced method, Inductive Coupled Plasma-Reactive Ion Etching(ICP-RIE). The etching conditions of ICP-RIE on CdZnTe substrate are explored and researched. First of all, a set of comparative experiments is designed. All of CdZnTe samples with the same component are polished by chemical mechanical polishing before etching. Then all samples are etched by different types of etching gases(CH4/H2/N2/Ar) and different ratios of gases as we designed. The etching time is all set to 30 minutes. After that, the surface roughness, etching rate, etching damage and the profile of etched mesas are tested and characterized by optical microscope, step profiler and confocal laser scanning microscope (CLSM), respectively. It is found that, Ar gas plays the role of physical etching, but the etching rate will decline when the concentration of Ar gas is too high. The results also show that, the introduction of N2 causes more etching damage. Finally, combination of CH4/H2/Ar is used to etch CdZnTe substrate. The ratio of these gases is 2sccm/2sccm/10sccm. The testing results of optimized etching show that, the maximum etching rate reaches up to 20μm/h and the etched CdZnTe surface is smooth with very low etching damage. At last, aimed at the shortcoming of photoresist’s degeneration after long-time etching, the ICP etching process of CdZnTe deep mesa is studied. Double-layer or triple-layer photoresist are spin-coated on CdZnTe substrate during the process of lithography. Then ICP etching is carried out with the optimized condition. It is seen that there is no more phenomena of degeneration.