Itching along with other problems can be one of the factors exacerbating the sufferings and disturbing the comfort of patients with chronic renal failure. The present research aimed to study the effects of omega-3 on the treatment of uremic pruritus in hemodialysis (HD) patients. In this crossover randomized clinical trial study, 52 HD patients with pruritus were evaluated. After the random assignment of the participants to Group 1 (treatment mode A) (omega-3 plus cetirizine) and Group 2 (treatment mode B) (cetirizine), they received the treatments for six weeks and then after one week washout period, treatments were changed between the two groups. The pruritus severity was measured using the Yosipovitch pruritus questionnaire before the intervention and at the end of each treatment period. The obtained data were analyzed using descriptive statistics, analysis of variance with repeated measures, and Pearson correlation coefficient. The results of this study showed that pruritus severity reduced in both groups, but it was more significant in Group 1 (omega-3 plus cetirizine). The study findings indicated that omega-3 is effective in the reduction of uremic pruritus. Therefore, this supplement can be used as a convenient method for reducing pruritus in HD patients.