Background: Emerging evidences suggested that LncRNA SNHG15 functioned as an oncogene to promote breast cancer (BC) progression, but the detailed mechanisms are still not fully delineated.Methods: The expression levels of the associated genes were examined by using the Real-Time qPCR and Western Blot. Dual-luciferase reporter gene system was performed to validated the potential targeting sites. Cell counting kit-8 and colony formation assay were used to measure cell proliferation, and trypan blue staining and Annexin V-FITC/PI double staining assay were performed to determine cell viability and apoptosis. Cell invasion and migration were examined by transwell and wound scratch assay, respectively. The tumor-bearing mice models were established, and immunohistochemistry (IHC) was conducted to examine expression and localization of Ki67 protein in tumor tissues.Results: Here we identified that LncRNA SNHG15 upregulated c-Myc to facilitate BC progression by sponging miR-451 in a competing endogenous RNA (ceRNA)-dependent manner in vitro and in vivo. Mechanistically, LncRNA SNHG15 and c-Myc were upregulated, while miR-451 was downregulated in BC cells and clinical tissues, compared to their normal counterparts. As expected, the Pearson correlation analysis results indicated that miR-451 negatively correlated with LncRNA SNHG15 and c-Myc, and LncRNA SNHG15 was positively relevant to c-Myc in BC tissues. Next, we validated that LncRNA SNHG15 sponged miR-451 to upregulate c-Myc in BC cells. Further gain- and loss-function experiments evidenced that LncRNA SNHG15 promoted, while miR-451 inhibited malignant phenotypes, including cell proliferation, viability, migration, invasion and epithelial-mesenchymal transition (EMT) in BC cells. Interestingly, the inhibiting effects of LncRNA SNHG15 ablation on BC progression were abrogated by both silencing miR-451 and overexpressing c-Myc.Conclusions: Collectively, the present study evidenced that targeting LncRNA SNHG15/miR-451/c-Myc signaling cascade was novel to hamper BC progression, and the potential underlying mechanisms were also uncovered, which broadened our knowledge in this field, and provided potential biomarkers for BC diagnosis and treatment.