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Background: This study aimed to investigate the effect of Bushen Yiqi Fuzheng decoction combined with sunitinib on the prognosis, clinical efficacy and immune function of patients with renal cell carcinoma (RCC) after surgery., Methods: A total of 120 patients who experienced RCC after surgery were randomly divided into the observation and control groups in this prospective study, with 60 cases in each group. The therapeutic effect, improvement of clinical symptoms, changes of immune function-related indicators and adverse reactions during medication were recorded. The changes in immune cell population, midkine (MK), interleukin 35 (IL-35), hypoxia-inducible factor 2alpha (HIF-2α), matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1), carcinoembryonic antigen (CEA), osteopontin (OPN), ferritin (FERR) and beta2-microglobulin (β2-MG) levels were measured. The Karnofsky performance status (KPS) score of patients was recorded., Results: The total effective rate of the observation group (95%) was better than that of the control group (85%, p < 0.05). After treatment, the changes of immune function indexes in the control group were not obvious. The indexes related to immune function in the observation group significantly decreased. Significant differences were observed in the cluster of differentiation 3+ (CD3+), cluster of differentiation 4+ (CD4+), cluster of differentiation 8+ (CD8+) and CD4+/CD8+ between the two groups after treatment. The incidence of adverse reactions in the observation group was lower than that of the control group. The KPS of the observation group was higher than that of the control group. Before treatment, no differences were observed in the MK, IL-35, HIF-2α, CEA, OPN, FERR, β2-MG, MMP-9 and TIMP-1 levels between the two groups. After treatment, the levels of the above parameters were lower than those before treatment, especially in the observation group., Conclusions: Bushen Yiqi Fuzheng decoction combined with sunitinib can significantly improve the clinical efficacy and postoperative immune function of RCC patients after surgery and down-regulate MMP-9 and TIMP-1 levels in the serum, which is beneficial to the prognosis of patients., Competing Interests: The authors declare no conflict of interest., (© 2023 The Author(s).)