Genetically modified tool animal models are the animal models, which are generated by modifying a defined gene and can be used as a tool to help realize other objective. Genetically modified large animals have wide applications in agriculture and biomedicine. Tool animal models play important role in biological research and development of new drugs in biomedicine,especially, have made tremendous contribution in revealing gene function and pathway of signal transduction.Pigs are not only an economically important agriculture animals, but also an ideal animal model in biomedicine due to its close similarity to human in physiology, as well as organ structure and size.Thanks to the breakthrough of newly emerged gene editing technology,striking progress has made in establishment of genetically modified tool pig models which include the ones used for monitoring pluripotency of cells, tracing cell lineages, replacing genes mediated by Cre recombinase, mimicking immunodeficiency,as well as gene editing in vivo.These tool models have been widely applied in biological research.Here, we will review the progress in generation of genetically modified tool pig models and their applications.