To investigate the therapeutic effects of the nuclear receptor subfamily 4 group A member 1(Nr4a1) agonist cytosporone B (Csn-B) on noise-induced hearing loss in mice. Methods: The HEI-OC1 outer hair cell line was subjected to hydrogen peroxide stimulation to establish an oxidative stress cell model. PCR was utilized to assess Nr4a1 expression in the cells. Cell viability was measured using CCK8, and flow cytometry was employed to evaluate apoptosis in cells pre-treated with Csn-B before hydrogen peroxide stimulation. By exposing mice to noisy audio, a model for noise-induced hearing loss was established, and PCR and immunofluorescence techniques were employed to detect Nr4a1 expression in the cochlea following noise exposure. ABR testing was conducted to assess mouse hearing both after noise exposure and following 13 days of continuous Csn-B treatment. Results: Nr4a1 expression increased in HEI-OC1 cells after hydrogen peroxide stimulation, accompanied by a significant decrease in cell viability and an increase in apoptosis. Pre-treatment with Csn-B enhanced cell viability and reduced apoptosis in HEI-OC1 cells exposed to hydrogen peroxide compared to the control group. In vivo studies revealed an increase in Nr4a1 expression in the cochlea of mice after noise exposure, associated with a decline in auditory function. Significant hearing recovery was observed after Csn-B treatment, evidenced by decreased thresholds in Click-ABR and Tone Burst-ABR (at 4000 and 8000Hz). Conclusion: The Nr4a1 agonist Csn-B enhances cellular resilience to oxidative stress and partially rescues noise-induced hearing loss in mice.