Objective To investigate the correlation of serum silence information regulator homolog 1 (SIRT1), peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) with serum inflammatory factors and hearing prognosis in patients with sudden deafness. Methods A total of 88 patients with sudden deafness admitted to the Second People’s Hospital of Mudanjiang City from May 2020 to May 2022 were taken as the study group, and divided into the good prognosis group and the poor prognosis group according to their hearing recovery. In addition, 82 healthy people who underwent physical examination in the hospital were collected as the control group. Serum levels of SIRT1, PGC-1α, inflammatory factor-tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and hypersensitive C-reactive protein (hs-CRP) were detected by enzyme-linked immunosorbent assay. Pearson method was adopted to analyze the correlation between serum levels of SIRT1, PGC-1α and inflammatory factors. Logistic regression analysis was applied to analyze the influencing factors of hearing prognosis.Results The proportions of patients with history of hypertension and diabetes in the study group were higher than those in the control group, the levels of SIRT1 and PGC-1α of the study group were significantly lower than those of the control group, and the levels of hs-CRP, IL-1β and TNF-α of the study group were obviously higher than those of the control group (all P<0.05). The level of SIRT1 in patients with sudden deafness was negatively correlated with the levels of hs-CRP, IL-1β and TNF-α (r=-0.524, -0.384, -0.542, all P<0.05), and the level of PGC-1α was negatively correlated with the levels of hs-CRP, IL-1β and TNF-α (r=-0.429, -0.457, -0.624, all P<0.05). In patients with sudden deafness, the levels of hs-CRP, IL-1β and TNF-α of the poor prognosis group were significantly higher than those of the good prognosis group, the levels of SIRT1 and PGC-1α of the poor prognosis group were obviously lower than those of the good prognosis group, and the proportions of patients with hypertension and diabetes of the poor prognosis group were higher than those of the good prognosis group (P<0.05). Logistic regression analysis showed that SIRT1, PGC-1α, hs-CRP, IL-1β, TNF-α, history of hypertension and history of diabetes were the influencing factors of hearing prognosis in patients with sudden deafness (P<0.05).Conclusion SIRT1 and PGC-1α are expressed at low level in the serum of patients with sudden deafness, and both are closely related to serum inflammatory factors and are influential factors for the prognosis of hearing.