Background: HER-2 positive breast cancer has a high risk of for relapse, metastasis and drug resistance, and is correlated with a poor prognosis. Thus, the study objective was to reveal target genes and key pathways in HER-2 subtype breast cancer. Methods: The gene expression dataset (GSE29431) was downloaded from the Gene Expression Omnibus database(GEO), and the differentially expressed genes (DEGs) were determined using LIMMA package in R software. Subsequently, Functional enrichment analysis were performed in ClusterProfiler package of R platform. The Search Tool for the Retrieval of Interacting Genes (STRING) database was used to construct a Protein-Protein Interaction (PPI) network of DEGs. Module analysis and target genes were identified by Cytoscape software. Further more, The influence of target genes on overall survival (OS) was assessed using the Kaplan-Meier plotter database.Results: The differential expression analysis revealed 96 genes were up-regulated while 407 genes were down-regulated in HER-2 positive breast cancer tissue compared to normal breast tissue. Functional enrichment analysis showed that the DEGs were mainly involved in regulation of lipid metabolic process, PPAR signaling pathway and PI3K-Akt signaling pathway. PPI network construction revealed a total of 199 nodes and 560 edges, and 12 target genes were identified by the highest value of degree. In addition, target genes were associated with worse overall prognosis, including NUSAP1, PTTG1, CEP55, TOP2A, CCNB1, CENPF, MELK, AURKA, UBE2C, BUB1B, KIF20A and RRM2.Conclusion: The present study identified 12 target genes associated with the development of HER-2 subtype breast cancer, which may help to provide new biomarkers and therapeutic targets.