Notably, the tumor first-order-10P was identified as the most influential feature in the model decision.<h4>Conclusions</h4>Our study suggests that the proposed automatic analysis framework based on 3D-CT multi-scale features has great potential for accurately predicting Ki67 expression levels in substantial RCC.<h4>Critical relevance statement</h4>Automatic analysis framework based on 3D-CT multi-scale features provides reliable predictions for Ki67 expression levels in substantial RCC, indicating the potential usage of clinical applications. This evidence concerns the gene MKI67 and renal cell carcinoma.