PURPOSE: Prediction of Fuhrman nuclear grade is crucial for making informed herapeutic decisions in clear cell renal cell carcinoma (ccRCC). The current study aimed to develop a multi-information fusion model utilizing computed tomography (CT)-based features of tumors and preoperative biochemical parameters to predict the Fuhrman nuclear grade of ccRCC in a non-invasive manner. METHODS: 218 ccRCC patients confirmed by histopathology were retrospectively analyzed. Univariate and multivariate logistic regression analyses were performed to identify independent predictors and establish a model for predicting the Fuhrman grade in ccRCC. The predictive performance of the model was evaluated using receiver operating characteristic (ROC) curves, calibration, the 10-fold cross-validation method, bootstrapping, the Hosmer-Lemeshow test, and decision curve analysis (DCA). RESULTS: R.E.N.A.L. Nephrometry Score (RNS) and serum tumor associated material (TAM) were identified as independent predictors for Fuhrman grade of ccRCC through multivariate logistic regression. The areas under the ROC curve (AUC) for the multi-information fusion model composed of the above two factors was 0.810, higher than that of the RNS (AUC 0.694) or TAM (AUC 0.764) alone. The calibration curve and Hosmer-Lemeshow test showed the integrated model had a good fitting degree. The 10-fold cross-validation method (AUC 0.806) and bootstrap test (AUC 0.811) showed the good stability of the model. DCA demonstrated that the model had superior clinical utility. CONCLUSION: A multi-information fusion model based on CT features of tumor and routine biochemical indicators, can predict the Fuhrman grade of ccRCC using a non-invasive approach. This model holds promise for assisting clinicians in devising personalized management strategies.