An enhancement in the expression of CISD2 in GC cells was significantly associated with a reduction in cell proliferation and tumor growth, inhibition of invasion and migration abilities, enhancement in the chemotherapeutic sensitivity to 5‐FU, and antagonism to 5‐FU‐induced autophagy through activation of the AKT/mTOR pathway in GC cells. The gene discussed is CISD2; the disease is gastric cancer.