Objective To study the application of autologous natural killer （NK） cells in the treatment of advanced renal cell carcinoma and the changes of immune function and tumor markers in patients. Methods 61 patients with advanced renal cell carcinoma admitted to Gansu Wuwei Tumour Hospital from March 2023 to April 2024 were divided into targeting group （31 cases， given supportive treatment combined with sunitinib malate capsules） and cell group （30 cases， autologous NK cells combined with targeting group） according to the patient 's willingness to treat combined with propensity score matching. 6 weeks was a treatment cycle， and all patients were treated for 4 cycles. The clinical efficacy of the two groups after 4 cycles of treatment and the occurrence of adverse reactions during treatment were statistically analyzed. The levels of serum cytokines， tumor markers， lymphocyte function and immune function were compared between the two groups before and after 4 cycles of treatment. Results After 4 cycles of treatment， the objective remission rate and disease control rate in the cell group were higher than those in the targeting group （P < 0.05）. After 4 cycles of treatment， the levels of serum hypoxia-inducible factor-1α （HIF-1α）， vascular endothelial growth factor （VEGF）， platelet-derived growth factor （PDGF）， carcinoembryonic antigen， carbohydrate antigen 125， carbohydrate antigen 199 and alpha-fetoprotein in the two groups were lower than those before treatment， and those in the cell group were lower than those in the targeting group （P < 0.012 5）. After 4 cycles of treatment， the levels of serum interleukin-2， interleukin-6， tumor necrosis factor-β， interferon-γ， peripheral blood CD3⁺， CD4⁺， NK cells and CD4⁺/CD8⁺in the two groups were higher than those before treatment. The levels of serum interleukin-2， tumor necrosis factor-β， interferon-γ， peripheral blood CD3⁺ and NK cells in the cell group were higher than those in the targeting group （P < 0.012 5）. The level of CD8⁺ in peripheral blood was lower than that before treatment （P < 0.012 5）， but there was no significant difference between the two groups （P > 0.012 5）. During the treatment， there was no significant difference in the incidence of diarrhea， nausea and vomiting， alopecia， liver function damage， decreased platelet level and decreased neutrophil level between the cell group and the targeting group （P > 0.05）. Conclusion The treatment of advanced renal cell carcinoma with autologous NK cells could improve the level of serum cytokines， reduce the level of tumor markers， regulate the function of lymphocytes and immune function， and had a good therapeutic effect. At the same time， it would not increase the incidence of adverse reactions， and the safety was good.