HOX proteins are a group of transcription factors, primarily associated with the role of regulators of anterior-posterior axis formation in early embryonic development. Because of their important role in developmental processes, they have remained highly conserved among members of animals with bilateral symmetry. Like other members of the Homeobox protein family, they contain a homeodomain, a three-dimensional structure that enables them to interact with regulatory DNA sequences. Their action is determined by the interaction with a large number of different groups of cofactors, which also belong to the Homeobox protein family and modulate the properties of HOX proteins, that is, their specificity and binding affinity of individual regulatory elements. As improperly formed patterns of HOX gene expression are often the cause of malformations and abnormalities in embryonic development, the correct expression of HOX genes is ensured by regulation through a large number of interconnected mechanisms. However, errors in the regulation of HOX gene expression are inevitable and, consequently, the occurrence of related pathological conditions, such as the development of some cancer types.