We synthesized new aroyl diheterocyclic pyrrole (ARDHEP) <b>15</b> that exhibited the hallmarks of ferroptosis. Compound <b>15</b> strongly inhibited U-87 MG, OVCAR-3, and MCF-7 cancer cells, induced an increase of cleaved PARP, but was not toxic for normal human primary T lymphocytes at 0.1 μM. Analysis of the levels of lactoperoxidase, malondialdehyde, lactic acid, total glutathione, and ATP suggested that the in vivo inhibition of cancer cell proliferation by <b>15</b> went through stimulation of oxidative stress injury and Fe<sup>2+</sup> accumulation. Quantitative polymerase chain reaction analysis of the mRNA expression in U-87 MG and SKOV-3 tumor tissues from <b>15</b>-treated mice showed the presence of <i>Ptgs2</i>/<i>Nfe2l2</i>/<i>Sat1</i>/<i>Akr1c1</i>/<i>Gpx4</i> genes correlated with ferroptosis in both groups. Immunofluorescence staining revealed significantly lower expressions of proteins Ki67, CD31, and ferroptosis negative regulation proteins glutathione peroxidase 4 (GPX4) and FTH1. Compound <b>15</b> was found to be metabolically stable when incubated with human liver microsomes.