The aim of the present study was to investigate the effects of RNA interference with prostaglandin-endoperoxide synthase 2 (COX‑2) gene on the proliferation and apoptosis of breast cancer MCF‑7 cells, as well as the underlying mechanism. The present study constructed the eukaryotic expression vector of the targeted COX‑2 gene, transfected the MCF‑7 cells and screened the stably expressed clone. Changes in the COX‑2 gene expression in breast cancer MCF‑7 cells prior to and following transfection were examined; the proliferation and apoptosis of MCF‑7 cells were analyzed. Furthermore, changes in the protein levels of survivin, B-cell lymphoma 2 (Bcl‑2) and Bcl-2-associated X (Bax) genes were detected. RNA interference mediated by a lentiviral expression vector significantly decreased the protein expression levels of the COX‑2 gene, and therefore, the proliferation and growth of breast cancer MCF‑7 cells was significantly suppressed and the apoptotic rate increased. Of note, the mRNA and protein expression levels of survivin and Bcl‑2 decreased, while those of Bax increased following COX-2 silencing. RNA interference markedly deactivated the COX‑2 gene, suppressed the proliferation of breast cancer MCF‑7 cells, and, to a certain extent, enhanced the induced spontaneous apoptosis, which is regulated by the Bax gene. These results provided evidence for the potential applications of RNA interference of the targeted COX‑2 gene in gene therapy for the treatment of breast cancer.