The talin proteins are a key component of the extracellular matrix-integrin-cytoskeleton system, and our previous study suggested that talin2 contributes to the tumor invasion and metastasis processes regulated by the tumor microenvironment. In the present study, the specific effects of talin2 on the invasive ability of breast cancer cells, as well as the underlying mechanism, were investigated by creating two MDA-MB-231 cell lines with stable talin2 knockdown by specific RNA interference. Initially, it was confirmed that the expression levels of talin2 in human breast cancer tissues were upregulated compared with in normal adjacent tissues. Subsequently, invasion and wound healing assays revealed that depletion of talin2 in MDA-MB-231 cells decreased their migratory and invasive abilities. Western blot analysis demonstrated that knockdown of talin2 in MDA-MB-231 cells caused marked downregulation of the tumor microenvironment markers hypoxia-inducible factor 1α, phosphorylated ribosomal protein S6 kinase, phosphorylated protein kinase B and phosphorylated mechanistic target of rapamycin. Furthermore, knockdown of talin2 decreased the basal contents of glucose and lactic acid in the breast cancer cell line. In conclusion, the findings of the present study demonstrated that talin2 knockdown may inhibit the invasive ability of human breast cancer MDA-MB-23l cells via alterations in the tumor microenvironment.