BACKGROUND: Although separate analysis of individual factor can somewhat improve the prognostic performance, integration of multimodal information into a single signature is necessary to stratify patients with clear cell renal cell carcinoma (ccRCC) for adjuvant therapy after surgery. METHODS: A total of 414 patients with whole slide images, computed tomography images, and clinical data from three patient cohorts were retrospectively analyzed. The authors performed deep learning and machine learning algorithm to construct three single-modality prediction models for disease-free survival of ccRCC based on whole slide images, cell segmentation, and computed tomography images, respectively. A multimodel prediction signature (MMPS) for disease-free survival were further developed by combining three single-modality prediction models and tumor stage/grade system. Prognostic performance of the prognostic model was also verified in two independent validation cohorts. RESULTS: Single-modality prediction models performed well in predicting the disease-free survival status of ccRCC. The MMPS achieved higher area under the curve value of 0.742, 0.917, and 0.900 in three independent patient cohorts, respectively. MMPS could distinguish patients with worse disease-free survival, with HR of 12.90 (95% CI: 2.443-68.120, P <0.0001), 11.10 (95% CI: 5.467-22.520, P <0.0001), and 8.27 (95% CI: 1.482-46.130, P <0.0001) in three different patient cohorts. In addition, MMPS outperformed single-modality prediction models and current clinical prognostic factors, which could also provide complements to current risk stratification for adjuvant therapy of ccRCC. CONCLUSION: Our novel multimodel prediction analysis for disease-free survival exhibited significant improvements in prognostic prediction for patients with ccRCC. After further validation in multiple centers and regions, the multimodal system could be a potential practical tool for clinicians in the treatment for ccRCC patients.