To explore the clinical effect of self-made addition and subtraction in the treatment of chronic renal failure complicated with skin lesions. Methods A total of 54 patients with chronic renal failure skin lesions admitted to our hospital from June 2022 to May 2023 were selected as the research objects. They were divided into control group and experimental group by random number table method, with 27 patients in each group. The control group was treated with routine treatment, and the experimental group was treated with self-made addition and subtraction (Zhiyang decoction). The therapeutic effect, skin symptoms, skin physiological state, TCM syndrome score and inflammatory factor level were compared between the two groups. Results The total effective rate of the experimental group was 96.30%, which was higher than 77.78% of the control group (P <0.05). After treatment, the scores of pruritus area, pruritus degree, pruritus accompanying symptoms, secondary skin lesions and TCM syndrome scores in the experimental group were lower than those in the control group (P <0.05). After treatment, the skin oil content and moisture content of the experimental group were higher than those of the control group (P <0.05). The levels of IL-6, CRP and TNF-α in the experimental group were lower than those in the control group (P <0.05). Conclusion The effect of self-made addition and subtraction on chronic renal failure complicated with skin lesions is satisfactory, which can improve the skin condition of patients and reduce the level of inflammatory factors.