To explore the application of comprehensive nursing intervention in hemodialysis patients with chronic renal failure and its improvement effect on pruritus. Methods A total of 60 hemodialysis patients with chronic renal failure admitted to Weihai Municipal Hospital Affiliated to Shandong University from March 2021 to March 2023 were randomly divided into control group and observation group, with 30 patients in each group. The control group was given routine nursing, and the observation group was given comprehensive nursing intervention. The improvement effect of pruritus, renal function index, negative emotions and nursing satisfaction were compared between the two groups. Results The total effective rate of skin pruritus improvement in the observation group was 96.67%, which was higher than 70.00% in the control group, and the difference was statistically significant (P <0.05). The levels of BUN and Cr in the observation group were lower than those in the control group after intervention, and the differences were statistically significant (P <0.05). After intervention, the scores of SAS and SDS in the observation group were lower than those in the control group, the differences were statistically significant (P <0.05). The nursing satisfaction of the observation group was 96.67%, which was higher than 73.33% of the control group, and the difference was statistically significant (P <0.05). Conclusion Comprehensive nursing intervention is effective in hemodialysis patients with chronic renal failure, which can reduce pruritus, relieve negative emotions, improve renal function and improve nursing satisfacti on.