As an important process in surface polishing of CZT substrate, the surface quality and production efficiency of CZT substrate are determined by the polishing results of CMP. Polishing fluid is one of the key influencing factors of CMP, which directly affects the surface quality of substrate after polishing. In this paper, the polishing liquid used in CMP process of CZT substrate is studied. The effects of silica sol and hydrogen peroxide on the surface quality and removal rate of the substrate are investigated under different pH values and abrasive concentrations. The results show that the high efficiency processing can be achieved by using the modified polishing liquid to perform CMP on CZT substrate while an ultra-smooth surface is obtained, which lays a good foundation for mass preparation of CZT substrate with high surface quality.