Sertraline showed potent anticancer effects against colorectal cancer in vitro and in vivoSertraline inhibited Akt‐ and STAT3‐driven proliferation but did not affect apoptosis, pyroptosis, ferroptosis, or mitophagySertraline induced autophagosome accumulation while blocking autophagic flux in colorectal cancer cells. The gene discussed is AKT1; the disease is colorectal cancer.