In this study, we revealed that OSCC cell-derived exosomes also activated the phosphorylation of p-38α, ERK1/2, JNK1/2, GSK-3α/β, and Akt and that pharmacological inhibitors of PI3K (LY294002), ERK-1/2 (PD98059), and JNK-1/2 (SP600125) abolished the tumor-promoting effects induced by OSCC cell-derived exosomes. The gene discussed is MAPK3; the disease is neoplasm.