Background <p>Breast cancer (BRCA) directly poses a threat to human life safety. This study aims to explore the role of lncRNA LEF1-AS1 in BRCA.</p> Methods <p>Firstly, the levels of LEF1-AS1 in tumor tissues and BRCA cells were detected by qRT-PCR. Furthermore, LEF1-AS1 was inhibited through cell transfection. Subsequently, the proliferation, apoptosis and migration abilities of the cells were detected using the CCK-8 assay, flow cytometry and Transwell assay. Meanwhile, the mRNA levels of epithelial-mesenchymal transition (EMT) markers were also measured. The targeting binding relationships between LEF1-AS1 and miR-328-5p, as well as between miR-328-5p and KLF16, were verified by dual luciferase reporter assays and RNA pull-down assays. Furthermore, the effects of co-regulating LEF1-AS1 and miR-328-5p and down-regulating KLF16 on tumor cells were further investigated.</p> Results <p>In tumor tissues and BRCA cell lines, LEF1-AS1 is highly expressed. Downregulation of LEF1-AS1 inhibits the malignant proliferation of BRCA cells and reduces their migration ability. Moreover, the process of EMT is significantly inhibited. miR-328-5p is the downstream target of LEF1-AS1. Simultaneously inhibiting miR-328-5p and LEF1-AS1 weakens the anti-cancer effect resulting from LEF1-AS1 silencing. LEF1-AS1 mainly participates in tumor progression by acting as a sponge molecule for miR-328-5p. Inhibiting LEF1-AS1 leads to the downregulation of KLF16, while the inhibition of miR-328-5p leads to the upregulation of KLF16. Moreover, the downregulation of KLF16 will result in weakened proliferation and migration abilities of BRCA cells.</p> Conclusions <p>LEF1-AS1 increases the level of KLF16 by sponging miR-328-5p, thereby promoting the proliferation, metastasis and EMT of BRCA cells.</p>