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Objective Hyperbaric oxygen treatment (HBOT) has demonstrated efficacy in improving hearing levels of patients with idiopathic sudden sensorineural hearing loss (ISSHL);however,the underlying mechanisms are not well understood.HBOT alleviates the inflammatory response,which is mediated by Toll-like receptor (TLR) 4 and nuclear factor (NF)-KB.In this study we investigated whether HBOT attenuates inflammation in ISHHL patients via alteration of TLR4 and NF-KB expression.Methods ISHHL patients (n =120) and healthy control subjects (n =20) were enrolled in this study.Patients were randomly divided into medicine group treated with medicine only (n =60) and HBO group receiving both HBOT and medicine (n =60).Audiometric testing was performed pre-and post-treatment.TLR4,NF-κB,and TNF-α expression in peripheral blood of ISSHL patients and healthy control subjects was assessed by ELISA before and after treatment.Results TLR4,NF-KB,and TNF-α levels were upregulated in ISSHL patients relative to healthy control subjects;the levels were decreased following treatment and were lower in the HBO group than that in the medicine group post-treatment (P ＜ 0.05 and P ＜ 0.01).Conclusion HBOT alleviates hearing loss in ISSHL patients by suppressing the inflammatory response induced by TLR4 and NF-KB signaling.