Background Early detection and accurate differentiation of malignant ground-glass nodules (GGNs) in lung CT scans are crucial for the effective treatment of lung adenocarcinoma. However, existing imaging diagnostic methods often struggle to distinguish between benign and malignant GGNs in the early stages. This study aims to predict the malignancy risk of GGNs observed in lung CT scans by applying two radiomics methods: topological data analysis and texture analysis. Methods A retrospective analysis was conducted on 3223 patients from two centers between January 2018 and June2023. The dataset was divided into training, testing, and validation sets to ensure robust model development and validation. We developed topological features applied to GGNs using radiomics analysis based on homology. This innovative approach emphasizes the integration of topological information, capturing complex geometric and spatial relationships within GGNs. By combining machine learning and deep learning algorithms, we established a predictive model that integrates clinical parameters, previous radiomics features, and topological radiomics features. Results Incorporating topological radiomics into our model significantly enhanced the ability to distinguish between benign and malignant GGNs. The topological radiomics model achieved areas under the curve (AUC) of 0.85 and 0.862 in two independent validation sets, outperforming previous radiomics models. Furthermore, this model demonstrated higher sensitivity compared to models based solely on clinical parameters, with sensitivities of 80.7% in validation set 1 and 82.3% in validation set 2. The most comprehensive model, which combined clinical parameters, previous radiomics features, and topological radiomics features, achieved the highest AUC value of 0.879 across all datasets. Conclusion This study validates the potential of topological radiomics in improving the predictive performance for distinguishing between benign and malignant GGNs. By integrating topological features with previous radiomics and clinical parameters, our comprehensive model provides a more accurate and reliable basis for developing treatment strategies for patients with GGNs.