Our previous research has established EZH2 as an oncogenic driver in the malignant transformation of oral leukoplakia and as an independent prognostic predictor for HNSCC patients.[42, 43] We have also elucidated mechanisms by which EZH2 expression is regulated in OSCC, including the role of lncRNA RC3H2 in sponging miR‐101‐3p to release EZH2 expression[44] and the action of lncRNA DUXAP9 in blocking CDK1‐mediated EZH2 degradation.[45] The present study unveils a novel mechanism that EZH2 undergoes degradation upon copper depletion. The gene discussed is EZH2; the disease is head and neck squamous cell carcinoma.