Compared to single-drug therapy, drug combinations have shown great potential in cancer treatment. Most of the current methods employ genomic data and chemical information to construct drug–cancer cell line features, but there is still a need to explore methods to combine topological information in the protein interaction network (PPI). Therefore, we propose a network-embedding-based prediction model, NEXGB, which integrates the corresponding protein modules of drug–cancer cell lines with PPI network information. NEXGB extracts the topological features of each protein node in a PPI network by struc2vec. Then, we combine the topological features with the target protein information of drug–cancer cell lines, to generate drug features and cancer cell line features, and utilize extreme gradient boosting (XGBoost) to predict the synergistic relationship between drug combinations and cancer cell lines. We apply our model on two recently developed datasets, the Oncology-Screen dataset (Oncology-Screen) and the large drug combination dataset (DrugCombDB). The experimental results show that NEXGB outperforms five current methods, and it effectively improves the predictive power in discovering relationships between drug combinations and cancer cell lines. This further demonstrates that the network information is valid for detecting combination therapies for cancer and other complex diseases.