Many kinds of typical crystal defects can be observed in the Cadmium Zinc Telluride (CdZnTe) single crystals. X-ray diffraction topography is a powerful method for investigating the structural integrity and homogeneity of single crystals. In this paper, the defects of CdZnTe substrate and Mercury Cadmium Telluride (MCT) epitaxial layer grown by liquid phase epitaxy (LPE) were investigated by X-ray diffraction topography in reflection. The X-ray diffraction topography and etched surface morphology of the same substrate were compared to characterize the defects. Six types of X-ray diffraction topography of defects in the CdZnTe substrate were observed including perfect structure, mosaic structure, twin crystals, low-angle grain boundary, inclusions/precipitates, and scratches. At present, most of the X-ray diffraction topographies of the samples show perfect structure of the CdZnTe substrates, free of scratches and mosaic structure defects. Low-angle grain boundary is the major type of defects in the CdZnTe substrates. Comparing the X-ray diffraction topography of CdZnTe substrate and MCT epitaxial layer grown on the same substrate by LPE, the low-angle grain boundary defects on the substrate were also observed on the MCT epitaxial layer. These results suggested that the quality of MCT epitaxial layer was closely related to the defects of CdZnTe substrate. The substrate with perfect structure was the foundation for the growth of MCT epitaxial layer with high quality.