Copy number variation (CNV) refers to the number of copies of a specific sequence in a genome and is a type of chromatin structural variation. The development of the Hi‐C technique has empowered research on the spatial structure of chromatins by capturing interactions between DNA fragments. We utilized machine‐learning methods including the linear transformation model and graph convolutional network (GCN) to detect CNV events from Hi‐C data and reveal how CNV is related to three‐dimensional interactions between genomic fragments in terms of the one‐dimensional read count signal and features of the chromatin structure. The experimental results demonstrated a specific linear relation between the Hi‐C read count and CNV for each chromosome that can be well qualified by the linear transformation model. In addition, the GCN‐based model could accurately extract features of the spatial structure from Hi‐C data and infer the corresponding CNV across different chromosomes in a cancer cell line. We performed a series of experiments including dimension reduction, transfer learning, and Hi‐C data perturbation to comprehensively evaluate the utility and robustness of the GCN‐based model. This work can provide a benchmark for using machine learning to infer CNV from Hi‐C data and serves as a necessary foundation for deeper understanding of the relationship between Hi‐C data and CNV.