KRAB-containing zinc-finger proteins (KRAB-ZFPs) first arose in the tetrapod vertebrates, and evolved quickly. Till Homo sapiens, they have become the largest family of transcription factors. Despite the molecular mechanism of transcription regulation by KRAB-ZFPs has been clarified in some degree, the higher-vertebrate-specific biological functions of the KRAB-ZFP family are still largely unknown. This review focused on the important regulatory functions of the KRAB-ZFP in embryonic development and tumorgenesis, which will benefit to the comprehensive understanding of biological roles of KRAB-ZFP in different physiological and pathological states. All of the systematic information will facilitate the further theoretical and applied studies of KRAB-ZFPs.