Recently, therapeutic peptides have demonstrated great promise for cancer treatment. To explore powerful anticancer peptides, artificial intelligence (AI)-based approaches have been developed to systematically screen potential candidates. However, the lack of efficient featurization of peptides has become a bottleneck for these machine-learning models. In this paper, we propose a topology-enhanced machine learning model (Top-ML) for anticancer peptide prediction. Our Top-ML employs peptide topological features derived from its sequence "connection" information characterized by vector and spectral descriptors. Our Top-ML model has been validated on two widely used AntiCP 2.0 benchmark datasets and has achieved state-of-the-art performance. Our results highlight the potential of leveraging novel topology-based featurization to accelerate the identification of anticancer peptides.