〔Abstract〕 Objective To investigate the efficacy of trepril combined with sunitinib in the treatment of advanced renal clear cell carcinoma and its effects on vascular endothelial growth factor (VEGF), growth differentiation factor 15 (GDF-15), and renal function. Methods A retrospective analysis was conducted on 20 patients with advanced renal clear cell carcinoma admitted to Zhangzhou Hospital Affiliated to Fujian Medical University from January 2019 to January 2021, who were treated with trepril combined with sunitinib. Analyze the patients' quality of life, serum VEGF, GDF-15 levels, renal function indicators, T lymphocyte subgroup levels, incidence of adverse reactions, and clinical efficacy. Results After treatment, the total effective rate of the patients' clinical efficacy was 60 %. After treatment, the serum levels of VEGF and GDF-15 in patients were lower than those before treatment, with statistically significant differences (P < 0.05). After treatment, the levels of serum creatinine (Scr), blood urea nitrogen (BUN), and urinary albumin (ALB) in patients were lower than those before treatment, with statistically significant differences (P < 0.05). Before and after treatment, there was no statistically significant difference in the levels of T lymphocyte subsets among patients (P > 0.05). After treatment, the patients' scores in the fields of physiology, psychology, social relations, and environment were higher than those before treatment, and the differences were statistically significant (P < 0.05). During the treatment period, the incidence of adverse reactions in patients was 35 % for hematological toxicity, 20 % for diarrhea, 30 % for loss of appetite, 20 % for fever, and 60 % for hair loss. Conclusion The combination of trepril and sunitinib has a significant therapeutic effect on advanced renal clear cell carcinoma, and can effectively improve the levels of VEGF, GDF-15, and renal function.