Background: Hemodialysis-related pruritus is a widespread, troubling issue with a complex pathogenesis, including neuropathy. The neurofilament light chain (NfL) is a neurocytoskeleton component that increases in neurodegenerative and polyneuropathy illnesses. Objectives: The aim of the current study was to evaluate the serum levels of NfL in pruritic hemodialysis patients. Patients and methods: Sixty patients receiving regular hemodialysis were selected, and divided into 2 equal groups (30 patients with pruritus, and 30 patients without pruritus), and a control group of 20 healthy individuals who were age and sex matched. With the help of the Visual Analogue Scale (VAS), pruritus intensity was evaluated. Hemoglobin, urea, creatinine, calcium, phosphorus, and parathormone laboratory tests were performed. Additionally, the serum NfL level was determined using ELISA. Results: Serum NfL levels varied significantly between the study groups (P=0.001), with pruritic hemodialysis patients having the highest median level, followed by those without pruritus, and the control group having the lowest level. There was a significant positive correlation between the duration and intensity of itching and blood NfL (P=0.001). Conclusion: Increased NfL levels in hemodialysis patients with pruritus support the neuropathy hypothesis as a source of pruritus in end-stage renal disease.