〔Abstract〕 To explore the role of semaphoring 6d ( SEMA6D) in the malignant progression of triple- negative breast cancer (TNBC) . Methods Bioinformatics and Immunohistochemistry (IHC) were used to analyze the expression level of SEMA6D in TNBC and paracancer non-tumor tissues and its relationship with patients ′clini- copathological features . MDA-MB-231 cell line stably knocking down the expression of SEMA6D was constructed , and the effects of SEMA6D on migration and invasion of TNBC cells were investigated by Wound-healing assays and Transwell assays . cBioPortal and GEPIA2 databases were used to screen out the gene negatively associated with it , namely aurora kinase A (AURKA) . Bioinformatics and IHC were used to analyze the expression level of AURKA in TNBC and paracancer non-tumor tissues and its relationship with patients ’clinicopathological features . Western blot assay was used to analyze the expression of AURKA and the effect of epithelial-mesenchymal transition (EMT) makers Claudin-1 , N-cadherin and Vimentin after knocking down SEMA6D . Results Bioinformatics analysis and IHC results showed that the expression of SEMA6D in TNBC tissues was significantly lower than that in paracancer non-tumor tissues (both P < 0. 05) . The expression of AURKA in TNBC tissues was significantly higher than that in paracancer non-tumor tissues (both P < 0. 05) , SEMA6D and AURKA were significantly negatively correlated in TNBC (P < 0. 01) . Both low expression of SEMA6D and high expression of AURKA were positively correlated with tumor size , tumor histological grade , clinical stage and lymph node metastasis in TNBC patients (all P < 0. 05) . The knockdown of SEMA6D significantly promoted the migration and invasion of ability TNBC cells ( both P < 0. 01) . Western blot results showed that the knockdown of SEMA6D upregulated AURKA expression , promoted the expression of N-cadherin and Vimentin , and inhibited the expression of Claudin-1 in tumor cells . Conclusion Down-regulation of SEMA6D expression in TNBC may be involved in the malignant progression of TNBC through up-regulation of AURKA expression and promotion of EMT.