Background Iron is required for the proliferation of cancer cells, and its depletion suppresses tumor growth. Eribulin mesylate (eribulin), a non-taxane microtubule inhibitor, disrupts the tumor microenvironment via vascular remodeling and obstruction of the epithelial-mesenchymal transition (EMT). Herein, we investigated the effects of the iron chelator deferoxamine (DFO) on tumor-related properties of breast cancer cells and the effects of DFO plus eribulin on tumor growth in vivo . Methods A triple-negative breast cancer (TNBC) cell line (MDA-MB-231) was used in our study. Cell proliferation, cell migration, cell cycle position, and gene expression were analyzed via MTT assays, wound-healing assays, flow cytometry, and quantitative real-time-polymerase chain reaction, respectively. For the in vivo experiments, mice with MDA-MB-231 xenografts were treated with the inhibitors, alone or together, and tumor volume was determined. Results DFO inhibited breast cancer cell proliferation and migration and decreased the proportion of S-phase cells. Conversely, it induced hypoxia, angiogenesis, EMT, and immune checkpoints, as determined by quantifying the expression of marker mRNAs. Eribulin suppressed the expression of the EMT marker mRNAs in the presence of DFO. DFO plus eribulin inhibited tumor growth in vivo to a greater extent than did either inhibitor alone. Conclusions Although DFO induces oncogenic events (hypoxia, angiogenesis, EMT, and immune checkpoints), it may be an effective treatment for breast cancer when administered in combination with eribulin.