We seek to know how metformin induces exosome biogenesis and secretion in cancer cells; and found that the mRNA level of genes related to exosome biogenesis and secretion such as Alix, Rab27b, CD81, CD63, and Lamp-2 concomitantly with CD63 protein level up-regulated in cells treated with metformin. The gene discussed is CD81; the disease is cancer.