The POU domain class IV family of transcription factors play essential roles in cellular differentiation and neural development, but its function in a regenerative context has not been thoroughly investigated. Using the freshwater planarian Schmidtea mediterranea, the present research identified pou4-2, a conserved homolog of pou4 downstream of soxB1-2, as an essential determinant of ciliated mechanosensory neuron fate. RNAi knockdowns of pou4-2 lead to loss of terminal differentiation markers in mechanosensory neurons, as well as defects in detecting water flow (rheosensation and vibration sensation, and these sensory modalities are not restored after regeneration. Analysis of the gene expression profile in pou4-2+ cells revealed a transcriptome comprised of many conserved genes involved in human auditory perception and vestibular sensation, suggesting that planarian mechanosensory neurons involved in rheosensation share similar functional properties with mammalian inner ear hair cells. Furthermore, RNAi experiments revealed mutual regulation between Pou4-2 activity and ephrin signaling. Thus, pou4-2 is a critical factor in the maintenance, differentiation, and regeneration of mechanosensory neurons in planarians.