Although similar LIF‐SEs have been identified as pivotal oncogenic SEs in osteosarcoma and esophageal adenocarcinoma, their biological roles and detailed mechanisms of action are still underexplored.[26, 37] We exploited the ABC model, HiChIP data analysis, and chemical intervention assays to establish that LIF was the primary transcriptional target of LIF‐SE rather than those genes in proximity in HNSCC. Here, LIF is linked to head and neck squamous cell carcinoma.