The neonatal mouse cochlea is able to regenerate lost sensory hair cells required for hearing. Here we found that levels of a transcription factor Sox2 modulates the level of hair cell regeneration at this developmental age. Moreover, Wnt signaling is a fundamentally important pathway that fuels regeneration in many tissues. We found that modulation of Sox2 enhances responsiveness to Wnt signaling. These results suggest a combinatorial approach is feasible and promising in modulating mammalian inner ear hair cell regeneration.