Sertraline sensitized TRAIL‐resistant lung cancer cells, upregulating DR5 and enhancing apoptosisIt inhibited autophagic flux via AMPK suppression, effects mimicked by autophagy inhibitorsDR5 silencing blocked the apoptosis, confirming its roleFindings suggest sertraline may be repurposed as a TRAIL‐sensitizing agent in lung cancer therapy. The gene discussed is TNFSF10; the disease is lung cancer.