GRP78 can promote the survival of head and neck cancer cells by maintaining lysosomal activity (Figure 1), meanwhile, through inhibiting the development of head and neck cancer by inducing a series of ubiquitination of mitochondrial ubiquitin ligase activator (such as MUL1, one of E3 ubiquitin-protein ligases) to down-regulate GRP78 (Table 1) (15). This evidence concerns the gene HSPA5 and head and neck cancer.