Abstract： Objective:To explore the clinical efficacy and mechanism of action of hyperbaric oxygen combined with Betahistine in the treatment of benign paroxysmal positional vertigo（BPPV）.Methods:A total of 116 BPPV patients admitted to Department of Neurology of Heping Hospital Affiliated to Changzhi Medical College from June 2021 to December 2022 were selected as the research subjects and assigned into observation group and control group according to the random number table method，with 58 cases in each group. The control group was treated with conventional symptomatic treatment combined with Betahistine，and the observation group was treated with hyperbaric oxygen on the basis of the treatment the control group. The scores of clinical symptoms and incidence of adverse reactions were compared between the two groups after treatment. The serum estradiol E2 levels before and after treatment were detected by electrochemiluminescence method，and serum otolin-1 levels before and after treatment were detected by enzyme-linked immunosorbent assay.Results:After treatment，the total clinical effective rate of the observation group（91.38%）was significantly higher than that of the control group（77.59%），and the difference was statistically significant（ χ2=4.209， P=0.040）. After treatment，the serum E2 level in the observation group was significantly higher than that in the control group，and the serum otolin-1 level was significantly lower than that in the control group（ P<0.05 or P<0.01）. The physical，functional，and emotional scores of the observation group were significantly lower than those of the control group after treatment（ P<0.01）. The total incidence of adverse reactions in the observation group（8.62%）was significantly lower than that in control group（27.59%），and the difference was statistically significant（ χ2=5.098， P=0.024）. Conclusion:Hyperbaric oxygen combined with Betahistine can effectively improve the clinical symptoms and the quality of life of the patients with BPPV，and the mechanism of action may be realized through alleviating the injury of inner ear by regulating the levels of serum E2 and otolin-1.