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Objective. To assess the effectiveness of comprehensive nursing in patients with chronic renal failure undergoing hemodialysis and the impact on their quality of life. Methods. The present study included 86 patients undergoing hemodialysis for chronic renal failure from January 2020 to October 2021 and randomly assigned them to receive either normal nursing or comprehensive nursing, with 43 cases in each group. Outcome measures included psychological status, treatment compliance, quality of life, and complications of the eligible patients. Results. After the intervention, comprehensive nursing resulted in lower Self-Rating Anxiety Scale (SAS) scores and Self-Rating Depression Scale (SDS) scores and higher quality of life scores for patients versus routine nursing ( P < 0.05 ). Comprehensive nursing was associated with a significantly higher overall patient compliance rate versus routine nursing ( P < 0.05 ). Patients receiving comprehensive nursing had a lower risk of developing complications versus those given routine nursing ( P < 0.05 ). Conclusion. Comprehensive care increases treatment compliance and self-care capacity of patients undergoing hemodialysis for chronic renal failure, improves their quality of life, and lowers the risk of complications, indicating a high potential for clinical advancement.