We investigated the effects of eribulin and paclitaxel on breast cancer (BC) by exploring molecular biomarkers and pathways. Co-expression networks were constructed by differentially co-expressed genes and links, and centralities were analyzed to explore the hub genes. Pathway-enrichment analysis was performed. The hub genes were validated using the polymerase chain reaction and western blotting. A total of 132 and 153 differentially expressed genes were identified in BC cell lines treated with eribulin and paclitaxel, respectively. Six hub genes were identified in two co-expression networks. The spliceosome pathway was the mutually significant pathway. The validation analysis was basically consistent with the bioinformatics. We successfully identified several hub genes and pathways relevant to the effects of eribulin and paclitaxel on BC based on the network analysis.