The purpose of this study was to evaluate whether induction of temporary threshold shift (TTS) with aspirin prior to cisplatin exposure can prevent or minimize cisplatin detrimental effects on hearing. We randomly divided BALB mice into three groups: (1) cisplatin only, (2) aspirin only, and (3) combined aspirin/cisplatin. Cisplatin was administered as a single intraperitoneal injection of 14mg/kg. Aspirin was administered for three weeks via intraperitoneal injection of 200mg/kg sodium salicylate, twice daily. Air conduction thresholds were recorded using Auditory Brainstem Responses (ABR). Cochleae were harvested and cochlear hair cells were counted using a scanning electron microscope (SEM). Aspirin-induced TTS have reached an average of 30.05±16.9dB after 2weeks. At 60days, cisplatin-only treated mice experienced an average threshold shifts of 50.7dB at 4kHz, 35.16dB at 8kHz, 70dB at 16kHz, 53.1dB at 32kHz. All threshold shifts were significantly worse than for cisplatin/aspirin treated mice with TTS of 11.85dB at 4kHz, 3.58dB at 8kHz, 16.58 dB at 16kHz, 20.41dB at 32kHz (p < 0.01). Cochlear cell count with SEM has shown reduction in the number of both inner and outer hair cells in the mid-turn in cisplatin treated mice. Aspirin induced TTS can protect from cisplatin-induced ototoxicity. This beneficial effect was demonstrated by auditory thresholds as well as SEM. Larger pre-clinical and clinical studies are still needed to confirm these findings.