AbstractObjectives/Hypothesis:To examine the effect of hepatocyte growth factor (HGF) for protection of auditory hair cells against aminoglycosides and its molecular mechanisms.Study Design:Experimental study.Methods:We quantitatively assessed protective effects of HGF on mouse cochlear hair cells against neomycin toxicity using explant culture systems. To understand mechanisms of hair cell protection by HGF, we examined the expression of c‐Met, HGF receptor, and 4‐hydroxynonenal (a lipid peroxidation marker) in the cochlea by means of immunohistochemistry and Western blotting.Results:The application of HGF to cochlear explant cultures significantly reduced the hair cell loss induced by neomycin. Immunohistochemistry showed c‐Met expression in normal auditory hair cells, and its increase in response to neomycin‐induced damage. Immunostaining for 4‐hydroxynonenal suggested that HGF acted by attenuating the lipid peroxidation of auditory epithelia induced by neomycin.Conclusions:These findings demonstrate that a functional HGF/c‐Met coupling is present in the cochlea, and HGF application exerts protective effects on hair cells, indicating the potential of HGF as a therapeutic agent for sensorineural hearing loss. Laryngoscope, 2009