Triple-negative breast cancer (TNBC) exhibits poor prognosis, with high metastasis and low survival. Long non-codingRNAs (lncRNAs) play critical roles in tumor progression. Here, we identified lncRNA MIR100HG as a pro-oncogene forTNBC progression. Knockdown of MIR100HG decreased cell proliferation and induced cell arrest in the G1 phase,whereas overexpression of MIR100HG significantly increased cell proliferation. Furthermore, MIR100HG regulated thep27 gene to control the cell cycle, and subsequently impacted the progression of TNBC. In analyzing its underlyingmechanism, bioinformatics prediction and experimental data demonstrated that MIR100HG participated in theformation of RNA–DNA triplex structures. MIR100HG in The Cancer Genome Atlas (TCGA) and breast cancer cell linesshowed higher expression in TNBC than in other tumor types with poor prognosis. In conclusion, our data indicated anovel working pattern of lncRNA in TNBC progression, which may be a potential therapeutic target in such cancers.