BACKGROUND: Triple negative breast cancer (TNBC) account for about 20% of breast carcinomas and the American society of clinical oncology guidelines does not specify approaches for TNBC patients since lack of specific driver molecules and targeted drugs. METHODS: We filtered out the aberrantly expressed mRNAs on the basis of RNA-seq data deposited in the Gene Expression Omnibus database, and verified and deeply analyzed screened differentially expressed genes (DEGs) using a combined bioinformatics approach. RESULTS: Of 21,755 genes with 472 TNBC cases from 3 independent laboratories, 159 mRNAs were identified as DEGs. To verify our results, we assessed the expression levels of top 8 DEGs in Oncomine database. The hierarchical clustering analysis, functional and pathway enrichment analysis were carried out for all DEGs. The results reveal that N-acetyltransferase 1 (NAT1) is most obvious of expression change's gene. Protein-protein interaction (PPI) network construction of 159 DEGs selected 3 hub genes: desmoglein 3 (DSG3), family with sequence similarity 83 member D (FAM83D) and GATA binding protein 3 (GATA3). For further analysis of the potential role of NAT1 in TNBC, the co-expression profiles of NAT1 in BC were made out, and we found that there are 5 genes [GATA3, trefoil factor 3 (TFF3), forkhead box A1 (FOXA1), signal peptide, CUB domain and EGF like domain containing 2 (SCUBE2), G protein-coupled receptor 160 (GPR160)] which co-expressed with NAT1 also were DEGs that we screened out before. Co-occurrence analysis confirmed that same as DEGs, GATA3 and SCUBE2 co-expressed with NAT1, and had a tendency towards a co-occurrence with NAT1 in TNBC. The survival curves showed that NAT1, GATA3 and SCUBE2 expression are significantly related with prognosis. CONCLUSIONS: From all above results, we speculate that NAT1, GATA3 and SCUBE2 play a vital role in TNBC.