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. Here, MTSS1 is linked to head and neck squamous cell carcinoma.