Peroxiredoxins are thiol-specific antioxidant proteins whose expression is elevated in several cancers. We compared the expression and function of Prdx1 and Prdx6 between the MCF-7 mammary adenocarcinoma cell line and the noncancerous MCF-10A cell line. We found elevated Prdx1 expression in MCF-7 cells and comparable expression of Prdx6. Suppression of Prdx1 and/or Prdx6 resulted in a modest increase in peroxide-induced cytotoxicity of MCF-7 cells, and a dramatic increase in MCF-10A cytotoxicity with and without hydrogen peroxide treatment. Our data confirm a cytoprotective role for peroxiredoxins and suggest a synergistic role for Prdx1 and Prdx6 in MCF-10A cells.