Hearing loss has become the most common sensory disorder worldwide. Despite intensive research on the pathophysiology of hearing loss, biological therapeutic approaches are limited by the anatomical and physiological characteristics of the inner ear. Challenges in inner ear drug delivery involve biotherapeutic instability, membrane inaccessibility and delivery non-specificity. With the development of nanotechnology, the nanoparticle-based delivery systems are promising to overcome these limitations. After drugs loading and stabilization, nanoparticles can carry the drugs into the inner ear by crossing round window membrane. The surface bioconjugation of ligand endows nanoparticles with specific targeting capability. Nanoparticles with stimuli-responsive moieties can provide a controlled release manner. Together, these strategies show great potential for hearing loss treatment. Understanding the current advances of nanotechnology in hearing loss treatment will facilitate future therapeutic options and clinical applications.