In recent studies, the focus on zebrafish, as a suitable laboratory model for studying vertebrate gene function, has increased dramatically. We evaluated the similarity between the three genes KLF2, MSX1 and SOX9 in humans and zebrafish. The KLF2 gene plays a role in heart and immunity of humans and zebrafish. In zebrafish, KLF2 gene is involved in immunogenesis and angiogenesis. This gene can increase the expression of thrombomodulin and endothelial nitric oxide synthase for human angiogenesis and vascular volume modulation. Zebrafish and human MSX genes are involved in the development of the ethmoid plate and are expressed in the neural crest and pre-placodal ectoderm. In zebrafish and humans, members of the SOX family play an important role in embryogenesis and sex determination. Therefore, understanding the relationship between zebrafish and human genes is important for effective modeling of human genetic diseases.