Amikacin is a frequently used antibiotic in the treatment of peritoneal dialysis (PD)-related peritonitis. Ototoxicity is a well-known complication of amikacin for which increased oxidative stress and free oxygen radicals are thought to be responsible. In this study, the effect of N-acetyl-cysteine (NAC) on cochlear function and oxidant situation in the amikacin related ototoxicity in PD-related peritonitis patients are investigated. Forty-six patients who had their first PD-related peritonitis attacks receiving empirical amikacin treatment were enrolled in the study. The patients were randomized into two groups; the first group (n = 23) as NAC receiving and the second group (n = 23) as a placebo receiving, control group. Otoacoustic emissions were measured before, 1 week after and 4 weeks after the treatment. Oxidative stress measurements were performed concurrently in order to evaluate the effectiveness of NAC. The results of screening with otoacoustic emission testing after amikacin treatment showed that cochlear function is protected especially in higher frequencies in NAC group when compared with the control group. Evaluation of the antioxidant status of the two groups showed no differences in the basal values, but at the first week there was an increase in the NAC group compared with the control group, and this increase became significant at the fourth week. NAC is found to be safe and effective in amikacin-related ototoxicity in patients with PD-related peritonitis. We suggest a close monitoring of the patients receiving amikacin containing treatment protocols and if amikacin is administrated supplementing the treatment with NAC.