The effectiveness of combining immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) in neoadjuvant therapy for renal cell carcinoma (RCC) remains unclear. This study aim to compare the efficacy and safety of neoadjuvant ICI plus TKI combination therapy versus TKI monotherapy in locally RCC patients. This study included 185 cases of locally RCC disease(TanyNanyM0) receiving neoadjuvant therapy from 29 centers across China from January 2019 to Feburary 2024. Primary endpoint was the objective response rate (ORR) in all patients and patients with tumor thrombus (TT). Secondary endpoints included recurrence-free survival (RFS), overall survival (OS), surgical outcomes, and safety. Statistical analysis was performed to compare the results between 2 groups. Combination therapy group had higher ORR compared to the TKI monotherapy group(30.9% vs. 16.3% in all patients, 34.5% vs. 15.6% in patients with TT) and pCR rate (14.8% vs. 0%). RFS rates were improved in patients with TT receiving combination therapy (P = .047). Furthermore, the combination therapy group had lower blood loss during surgery (200 mL vs. 300 mL, P = .004). The main limitation is the retrospective study design. Neoadjuvant ICI plus TKI combination therapy showed promising efficacy and acceptable toxicity. These findings suggest that further investigation is warranted to explore the potential of this treatment approach.