Triple‑negative breast cancer (TNBC) is characterized by fast progression with high potential for metastasis, and poor prognosis. The dysregulation of microRNAs (miRNAs) occurring in the initiation or progression of cancers often leads to aberrant gene expression. The aim of the present study was to explore the function of miR‑126 in TNBC cells. Expression levels of miR‑126‑3p were determined by quantitative real‑time PCR. Then, the effects of miR‑126‑3p on migration, proliferation, invasion, and angiogenesis were assessed through in vitro experiments including Cell Counting Kit‑8, colony formation, Transwell invasion and vasculogenic mimicry formation assays. One of the target genes for miR‑126‑3p predicted by TargetScan was confirmed by luciferase activity assay. Results indicated that miR‑126‑3p expression was reduced in TNBC cell lines. Functional assays revealed that miR‑126‑3p overexpression inhibited cell proliferation, migration, invasion, colony formation capacity and vasculogenesis by 1.2‑, 1.8‑, 2.3‑, 2.0‑ and 3.3‑fold, respectively, compared to the miRNA‑negative control group of MDA‑MB‑231 cells (P<0.001, respectively). In addition, the regulator of G‑protein signaling 3 (RGS3) was hypothesized and validated as a direct target of miR‑126‑3p in TNBC. The proliferation, migration, invasion, colony formation capacity and vasculogenesis of MDA‑MB‑231 cells were significantly increased by 1.4‑, 2.0‑, 1.8‑, 1.4‑ and 3.2‑fold, respectively, in cells transfected with pcDNA3.0‑RGS3 compared to pcDNA3.0‑negative control groups (P<0.001, respectively). The influence of miR‑126‑3p expression was reversed by RGS3 restoration. Collectively, the present study revealed that miR‑126‑3p plays a role as a tumor suppressor in regulating TNBC cell activities by targeting RGS3, indicating that the miR‑126‑3p/RGS3 axis may be a potential treatment target.