Recent studies have reported an association between chronic renal failure and hearing impairment. Yet, the exact mechanism of action is still not fully understood. In this study, we investigated the expression of fibroblast growth factor 23 (FGF23) and D-serine in maintenance hemodialysis (MHD) patients with end-stage renal disease (ESRD) complicated with hearing impairment and further investigated the correlation between FGF23/D-serine and hearing impairment.A total of 90 subjects, including 30 MHD patients complicated with hearing impairment, 30 MHD patients with normal hearing, and 30 controls, were included in this case-control study. Relevant data were obtained by questionnaire survey, audiometric test, enzyme-linked immunosorbent assay (ELISA) to determine FGF23 level, and high-performance liquid chromatography to determine D-serine level.MHD patients showed abnormally high expression of FGF23 and D-serine, where FGF23 and D-serine levels were significantly higher in the group with hearing impairment than in the group with normal hearing and normal controls (all P<0.01). Also, elevated FGF23 and D-serine were identified as risk factors for hearing impairment in ESRD, with ORs of 16.54 (95%CI, 2.75-99.55) and 15.22 (95%CI, 2.59-89.51), respectively. Further Person correlation analysis showed a moderate positive correlation between FGF23 and D-serine (r = 0.683, P<0.001).This study provides potential biomarkers for the early detection of hearing impairment complicated by chronic renal failure, and the reduction of FGF23/D-serine may provide a potential target for the treatment of hearing impairment complicated by chronic renal failure.Copyright: © 2023 Yuan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.