Abstract: The proteins with ^'homeobox^'(HOX) domain, a large family of DNA binding, play an important role in embryonic development, gene regulation, cell differentiation and neurogenesis. Some other domains are found in the proteins together with HOX, such as PAX, POU, LIM, OAR, ELK, SIX, bZIP, PHD-finger, Engrailed, hexapeptide domains. The HOX combined with other domains that associate with DNA binding or protein interactions are called “complex homeobox”. Recent reports indicate that “complex homeobox” genes also take part in tumorigenesis by the way of gene fusions and deregulation. The progress of “complex homeobox” in types, structures and functions have been summarized in this review.