Indeed, LIF is a pleiotropic cytokine that regulates stemness in normal stem cell and CSC contexts.[24, 47] Consistent with these previous results, our results revealed that LIF functioned as a potent factor to maintain CSCs self‐renewal and expansion in HNSCC as evidenced by the following facts: rhLIF exposure promoted tumorsphere formation and CSC markers expression; LIFR knockdown impaired stemness and CSCs proportions; chemical inhibitions of LIFR or STAT3 significantly reduced BMI1 and SOX2 expression in PDO models. This evidence concerns the gene BMI1 and head and neck squamous cell carcinoma.