Breast cancer(BC) is the most frequent cancer type in women. However, the pathogenesis of BC is still not well understood. Thus, we aim to explore key genes and pathways in relation to BC. We used the Gene Expression Omnibus (GEO) database to identify the differently expression of genes in the carcinogenesis and progression of BC. Then, bioinformatics analysis was performed to determine the key genes targets and pathways associated with BC. The gene expression profile of the hub genes in human tumor was displayed using GEPIA. Finally, the expression of hub genes, correlation between genes and miRNA were screened via the miRDB, MirTarBase and DIANA Tools. We screened 159 downregulated genes and 55 upregulated genes in BC patients among the 4 datasets. The enriched functions of the DEGs involved in cell proliferation, positive regulation of Akt signaling and extracellular exosome, PPAR signaling pathway and AMPK signaling pathway. 3 hub genes were screened out by construction of PPI network. MELK were found to be upregulated, and CLU and NTRK2 were downregulated. Further verification showed that MELK displayed higher levels in almost all tumors. We found correlation between these hube genes and the miRNAs. All in all, three key genes closely related to the incidence of BC were identified, and the results could provide new potential molecular targets for the diagnosis and treatment of BC. In particular, MELK is regulated by multiple miRNAs and participate in the development of BC.