Background. End-stage renal disease (ESRD) patients often experience hearing impairment, resulting in a high rate of disability and a decline in their quality of life. Fibroblast growth factor-23 (FGF23) is a diagnostic biomarker for chronic kidney disease (CKD) and a pathogenic contributor to CKD progression. However, the correlation between FGF23 level and CKD patients with hearing impairment remains elusive. This study aimed to investigate the relationship between the FGF23 and ESRD accompanied with hearing impairment. Methods. A total of 144 ESRD patients, who were admitted to the First Affiliated Hospital of Kunming Medical University from November to December 2020, were enrolled in this study. Firstly, 144 ESRD patients underwent pure-tone audiometry (PTA). Secondly, it was attempted to randomly select 20 ESRD patients with normal hearing, and 20 ESRD patients with hearing impairment (match ratio, 1:1). Age and gender-matched healthy people (n = 20) were also recruited as controls group. The expression levels of FGF23 was detected by enzyme-linked immunosorbent assay (ELISA). Results. The results of pure-tone audiometry showed that the prevalence of hearing impairment in ESRD patients was 80.5%. Male ESRD patients were more likely to develop hearing impairment compared to female patients. The incidence rate of hearing impairment at a high frequency was significantly higher than that at a low frequency (P < 0.01). The serum levels of FGF23, phosphorus, and parathyroid hormone (PTH) in ESRD patients with hearing impairment significantly increased compared with those with normal hearing and healthy controls. Conclusion. ESRD patients had a higher risk of hearing loss, especially high-frequency hearing impairment. As FGF23 level increased, the risk of hearing loss was also elevated. The hearing impairment in ESRD patients was associated with the degree of kidney injury, and serum FGF23 level.