Abstract Purpose Long noncoding RNAs (lncRNAs) are oncogenic or tumor suppressor biomolecules that play an important role in the progression of human tumors. In the current study, we aimed to explore the effect of targeting oncogenic lncRNA SIRLNT (SIRT1 regulating lncRNA tumor promoter) as the most significantly up-regulated lncRNA in human breast cancer cells. Methods Locked nucleic acid (LNA) GapmeRs antisense oligonucleotides were used to knock down lncRNA SIRLNT expression. MCF-7 cell line was used to investigate the effect of antisense lncRNA SIRLNT on SIRLNT lncRNA knockdown. MCF7 cell line was transfected with SIRLNT antisense LNA GapmeRs at three different time points. Quantitative real-time PCR (qRT-PCR) was used to evaluate the expression of lncRNA SIRLNT and SIRT1 (as a molecule under the influence of lncRNA SIRLNT). The viability of cells was assessed by MTT assay, and the apoptosis and necrosis were measured by FITC Annexin V Apoptosis Detection Kit with PI staining assay. Results The results showed that lncRNA SIRLNT knockdown could inhibit cell proliferation and also lead to apoptosis and necrosis of the MCF-7 cell line. qRT-PCR results indicated SIRT1 was significantly upregulated in lncRNA SIRLNT knockdown cells as a tumor suppressor. Conclusion Our finding suggested that lncRNA SIRLNT inhibition could be a promising therapeutic strategy to prevent the progression of breast cancer.