In the present study, we showed that restoring TIPE3 interacted with the MIM ETC complex, disrupted the mitochondria membrane and enhanced permeability (represented as obscure cristae, mitochondrial membrane potential depolarization, and increased round mitochondria [25, 33]), and induced mitochondria dysfunction (represented as OXPHOS and ATP generation decrease and ROS accumulation [25, 33]) in HNSCC cells. The gene discussed is TIPE3; the disease is head and neck squamous cell carcinoma.