Polyethyleneimine-polyethylene glycol (PEI-PEG), a novel nanocarrier, has been used for trans-fection and gene therapy in a variety of cells. In our previous study, we successfully carried out PEI-PEG-mediated gene transfer in spiral ganglion cells. It remains unclear whether PEI-PEG could be used for gene therapy with X-linked inhibitor of apoptosis protein (XIAP) in the inner ear. In the present study, we performed PEI-PEG-mediated XIAP gene transfection in the cochlea of Sprague-Dawley rats,via scala tympani fenestration, before daily cisplatin injections. Audito-ry brainstem relfex tests demonstrated the protective effects ofXIAP gene therapy on auditory function. Immunohistochemical staining revealed XIAP protein expression in the cytoplasm of cells in the spiral ganglion, the organ of Corti and the stria vascularis. Reverse transcription-PCR detected high levels ofXIAP mRNA expression in the cochlea. The present ifndings suggest that PEI-PEG nanocarrier-mediatedXIAP gene transfection results in XIAP expression in the cochlea, prevents damage to cochlear spiral ganglion cells, and protects hearing.