Transcription factors have the fundamental function of recognizing and binding to DNA sequences and controlling gene expression. They play an important role in many intracellular reactions by activating or inactivating gene transcription. The expression of various cell-specific genes is regulated by a combinatorial code of transcription factors. As transcription factors are usually involved in the activation of multiple genes, they often cause syndromic hearing loss, which causes other symptoms in addition to hearing loss. EYA1 and SIX1 are involved in the differentiation of the second branchial arch (and kidney) as well as the differentiation of the ear, causing BO(R) syndrome. PAX3, SOX10, MITF, and SNAI2 are known to act as transcription factors that promote melanocyte differentiation and migration. Pathogenic variants in PAX3, SOX10, MITF, EDNRB, EDN3, and SNAI2 were identified as responsible genes for Waardenburg syndrome, which is associated with pigmentary abnormalities in various organs (hair, iris, and skin) and sensorineural hearing loss. CHD7, which plays a crucial role in the development of multipotent migratory neural crest, is known as a main cause of CHARGE syndrome. POU3F4, known as the most prevalent gene responsible for X-linked sensorineural hearing loss, plays a critical role in the development of the middle and inner ear. Patients with the POU3F4 variant are characterized by an inner ear malformation known as incomplete partition of the cochlea type 3 (IP-III). POU4F3 is a transcription factor essential for the development and survival of inner ear hair cells and is expressed exclusively in hair cells in the inner ear. Patients with the POU4F3 variant present with late-onset, progressive hearing loss (DFNA15). EYA4 is a transcriptional factor and is considered to be required for the maturation and maintenance of the organ of Corti. Variants in EYA4 are known to cause late-onset, progressive hearing loss with or without mild abnormalities in electrocardiograms (DFNA10).