At this time, we determined that POLE2 knockdown inhibited, while POLE2 overexpression activated the NRF2/GPX4 pathway in human gastric cancer cells, and that either NRF2 or GPX4 silence blocked POLE2 overexpression‐mediated inductions of cell proliferation, migration, invasion and inhibition of ferroptosis. The gene discussed is POLE2; the disease is gastric cancer.