Although the underlying mechanisms by which EZH2 regulates MICU1 to prevent HNSCC cell apoptosis is not entirely clear, our data showed inhibiting EZH2 triggers cyto-Ca2+ accumulation, loss of ΔΨm, G1 phase cell cycle arrest and changes on proteins of mitochondrial related cell death pathway. This evidence concerns the gene MICU1 and head and neck squamous cell carcinoma.