Objective To observe the clinical effect of Shenmai injection combined with hyperbaric oxygen in the treatment of sudden deafness (SD), and explore the mechanism of treatment, so as to provide theoretical basis for clinical treatment of sudden deafness. Methods A total of 206 SD patients in the Otolaryngology Department of Taihe Hospital between January 2015 and March 2016 were selected. According to the order of admission they were randomly divided into observation group and Shenmai group. The patients in the observation group were given conventional treatment with Dexamethasone and Vinpocetine. The patients in the Shenmai group were treated with intravenous infusion of Shenmai injection combined with hyperbaric oxygen in addition to conventional treatment. The auditory brainstem response (ABR) threshold was recorded, and the latency of wave I-VI was recorded during 80 dB nHL short wave stimulation. Venous oxygen saturation (SvO2) was analyzed. Noninvasive transcranial Doppler was used to record regional cerebral blood flow (RCBF). The residual rate, healing rate and total effective rate of tinnitus and vertigo before and after treatment in the two groups were statistacally analyzed. Results Compared to the observation group, the latency of ABR wave II and III, wave I-III interval, and ABR threshold significantly decreased in the Shenmai group (P < 0.05), while SvO2 and RCBF increased in the Shenmai group (P < 0.05). The residual rate of tinnitus and vertigo decreased markedly, the healing rate was 79.61%, the total effective rate was 98.05%, compared with the observation group, the differences were statistically significance (P < 0.05). Conclusions Shenmai injection can improve the blood flow of the damaged cochlea tissue. Hyperbaric oxygen can increase SvO2 and the perilymphatic oxygen pressure, and promote the repair of cochlea and vestibular nerve. Combination of Shenmai injection with hyperbaric oxygen can obviously improve the curative effect of SD.