In this study, by analyzing mTORC1-activated mouse embryonic fibroblasts (MEFs) and cancer cells, laryngeal squamous cell carcinoma (LSCC) clinical samples, LSCC patient–derived organoids (PDO), and LSCC patient–derived xenograft (PDX) models, we established that endoplasmic reticulum oxidoreductase 1 alpha (ERO1α) is involved in hyperactivated mTORC1-mediated ferroptosis resistance and tumor growth. The gene discussed is ERO1A; the disease is cancer.