<p>Breast cancer is one of the most prevalent cancers among women, often attributed to genetic mutations, hormonal imbalances, and lifestyle factors. The compound benzo[α]pyrene (B[α]P) is commonly found in emissions and fumes from industrial processes and cigarette smoke. Punicalagin (PCG), a polyphenolic compound in pomegranates, is reported to have antioxidant, anti-inflammatory, anti-cancer, and antiviral activities. In this study, we aimed to determine whether B[α]P induced toxicity in breast cancer cells and to assess the role of PCG in mitigating this toxicity. The water-soluble tetrazolium salt (WST) assay showed that exposure of MDA-MB-231 and MCF-7 cells to B[α]P at 1–32&#xa0;µM decreased their viability. B[α]P also resulted in the decrease of the mitochondrial membrane potential in both cell lines. The change in mitochondrial reactive oxygen species levels was confirmed using MitoSOX™ staining of MDA-MB-231 and MCF-7 cells, and the level of red fluorescence increased upon exposure to B[α]P compared to the control group. In the scratch wound healing and transwell migration assays, B[α]P induced migration of MDA-MB-231 cells, which was mitigated by PCG. Furthermore, there was an increase in the N-cadherin expression and a decrease in the E-cadherin expression on exposure to B[α]P. However, PCG reversed this trend. Our findings suggest that PCG mitigates B[α]P-induced mitochondrial dysfunction, oxidative stress, and epithelial-mesenchymal transition, thereby reversing B[α]P’s pro-tumorigenic effects in breast cancer cells.</p> Graphical Abstract <p></p>