Objectives: Triple negative breast cancer cells are estrogen, progesterone, and HER receptor negative, malign breast cancer cells. These cells have high telomerase activity, and this activity gives these cells high proliferation and evading apoptosis abilities. In this study, we aimed to determine the affect piR-823 on genetic parameters of proliferation and ER alpha status in MDA-MB-231 cells. Methods: After anti-piR-823 transfection, proliferation of cells was tested by XTT. Gene expressions were determined by RT-PCR. Protein expressions were determined by ELISA. Results: The proliferation decreased after inhibition (p<0.001). Gene and protein expressions of ERa were upregulated while hTERT was downregulated after inhibition (p<0.001). Furthermore, piR-823 inhibition cause to decrease PI3K/ AKT/mTOR gene expressions and miR-126 expression (p<0.001). Conclusion: Obtained data indicates that piR-823 inhibition lead MDA-MB-231 cells to increase ERa expression. Decreased expressions of hTERT and PI3K/AKT/mTOR pathway affect cell proliferation. Moreover, miR-126 decrease indicates that piRNAs and miRNAs can share the same target molecules and piRNA expression changes might have an impact on miRNA expressions. All obtained data is important on the perspective of piRNAs and their effect on cellular characteristics of triple negative breast cancer cells.