Objective：To study the effect of aspirin（ASA） on the expression of heme oxygenase-1（HO-1） in cochlear spiral ganglion neurons（SGNs） of guinea pigs with cisplatin（DDP） ototoxicity，and to explore the protective effect of ASA on cochlear SGNs of guinea pigs with DDP ototoxicity by inducing the expression of HO-1. Methods：Forty guinea pigs were randomly and equally divided into 4 groups：group A（normal control group） received intraperitoneal injection of 0.9% normal saline at a daily dose of 10 mL/kg；group B （DDP group） received intraperitoneal injection of DDP at a daily dose of 10 mg/kg；group C（ASA+DDP group） received in－traperitoneal injection of DDP at a daily dose of 10 mg/kg following 1-hour pretreatment of 100 mg/kg ASA；group D [HO-1 inhibitor zinc protoporphyrin IX（ZnppIX）+ASA+DDP group] received intraperitoneal injection of DDP at a daily dose of 10 mg/kg following 1-hour pretreatment of 10 μmol/kg ZnppIX and 100 mg/kg ASA. Each group received treatment once in the morning and once in the evening. After 10 days of continuous administration，changes in auditory brainstem response（ABR） threshold were observed in each group. The HO-1 expression in cochlear SGNs was measured by immunohistochemistry，immunofluorescence，and Western blot. Results：In all the four groups，group D had the highest ABR threshold（47.18±2.56），followed by group B（39.98±7.32），group C （2.85±2.38），and group A（1.65±2.13）. The immunohistochemistry and immunofluorescence results showed that group A had the highest HO-1 expression，followed by group C，group B，and group D. The Western blot results showed that there were significant dif－ferences between the four groups in HO-1 expression（P=0.000） and group A had the highest expression（0.98±0.07），followed by group C（0.63±0.02），group B（0.27±0.05），and group D（0.12±0.09）. Conclusion：ASA can protect SGNs from DDP-induced oto－toxicity by increasing the expression of HO-1 in cochlear SGNs.