Objective: To observe the efficacy of dexamethasone injection assisted betahistine in the treatment of patients with sudden deafness. Methods: Sixty patients with sudden deafness admitted to our hospital from July 2022 to August 2024 were selected as the study objects. Patients were divided into control group and observation group by random number table method, with 30 cases in each group. The control group was treated with betahistine. The observation group was treated with dexamethasone injection and betahistine. The therapeutic effect, hearing level, symptom improvement, hemorheology [high whole blood viscosity (HS), plasma viscosity (PV), low whole blood viscosity (LS), erythrocyte specific volume (HCT)], serum related factors [homocysteine (Hcy), endothelin-1 (ET-1), calcitonin gene-related peptide (CGRP), vascular endothelial growth factor (VEGF)] levels and adverse reactions of the two groups were analyzed and compared. Results: The total effective rate of observation group was significantly higher than that of control group (P < 0.05). After 14 days of treatment, the pure tone hearing threshold of both groups was significantly lower than that before treatment, and the pure tone hearing threshold of the observation group was significantly lower than that of the control group. After 14 days of treatment, the disappearance time of clinical symptoms of vertigo, tinnitus and ear distention in observation group was significantly shorter than that in control group (P < 0.05). After 14 days of treatment, HS, PV, HCT and LS in both groups were significantly lower than before treatment, and HS, PV, HCT and LS in the observation group were significantly lower than those in the control group (P < 0.05). After 14 days of treatment, Hcy, ET-1 and VEGF in both groups were significantly lower than before treatment, and CGRP was significantly higher than before treatment (P < 0.05). The changes of Hcy, ET-1, VEGF and CGRP in observation group were significantly greater than those in control group (P < 0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P > 0.05). Conclusion: Dexamethasone injection assisted betahistine in the treatment of sudden deafness can improve the therapeutic effect, improve the hearing level of patients, alleviate clinical symptoms, improve hemorheology and vascular endothelial function, and has good safety.