BRCA is the most common malignancy that poses a serious threat to women’s health, and metastasis is the leading cause of death for patients with BRCA.37 In the present study, we investigated the role of SLFN5 in BRCA progression using bioinformatic tools, gain or loss of expression, ChIP-Seq analyses and ZEB1 promoter activity assays, and we clearly demonstrated that human SLFN5 is a breast cancer suppressor, and that its anti-oncogenic functions are realised through a direct modulation of ZEB1 expression in breast cancer. Here, SLFN5 is linked to breast carcinoma.