Objective: Twenty HDPs were enrolled from a single hospital. Their visual analog scale (VAS) and Shiratori scores were measured before treatment, during 4 weeks of treatment, and after treatment. Skin inflammatory cytokine and blood calcium/phosphate/vitamin D levels were measured before and after 4 weeks of treatment. Methods: The VAS and Shiratori scores were significantly reduced in both the nalfurafine and NB-UVB treatment groups. (Figure 1) After 4 weeks of treatment, the NB-UVB treatment group maintained a low Shiratori score. However, the nalfurafine treatment group showed increased Shiratori scores again. The calcium phosphate product concentration was increased in the NB-UVB treatment group and decreased in the nalfurafine group. (Figure 2) The vitamin D level was increased only in the NB-UVB treatment group. The skin inflammatory cytokine levels showed a decreasing trend in both groups but not statistically significantly. No side effects were observed in both treatment groups. Results: Nalfurafine, an oral medication, could be an alternative treatment option comparable with NB-UVB for severe pruritus in HDPs. Conclusions: Objective: Pruritus in hemodialysis patients (HDPs) is a serious complication associated with the quality of life and psychiatric disorder of patients. Only a few treatment options are available for pruritus, and their effectiveness is controversial. We designed this study to compare nalfurafine hydrochloride, a kappa-opioid receptor agonist, with narrow-band ultraviolet B phototherapy (NB-UVB) in HDPs. Methods: Twenty HDPs were enrolled from a single hospital. Their visual analog scale (VAS) and Shiratori scores were measured before treatment, during 4 weeks of treatment, and after treatment. Skin inflammatory cytokine and blood calcium/phosphate/vitamin D levels were measured before and after 4 weeks of treatment. Results: The VAS and Shiratori scores were significantly reduced in both the nalfurafine and NB-UVB treatment groups. (Figure 1) After 4 weeks of treatment, the NB-UVB treatment group maintained a low Shiratori score. However, the nalfurafine treatment group showed increased Shiratori scores again. The calcium phosphate product concentration was increased in the NB-UVB treatment group and decreased in the nalfurafine group. (Figure 2) The vitamin D level was increased only in the NB-UVB treatment group. The skin inflammatory cytokine levels showed a decreasing trend in both groups but not statistically significantly. No side effects were observed in both treatment groups. Conclusions: Nalfurafine, an oral medication, could be an alternative treatment option comparable with NB-UVB for severe pruritus in HDPs.