In the present study, we demonstrated that frugoside: (a) Inhibited Srx expression and subsequently delayed the reduction of hyperoxidized Prxs in melanoma cells, (b) regulated mitochondrial function, (c) induced ROS generation and p38 MAPK activation, and (d) consequently induced mitochondria-mediated apoptotic cell death in melanoma cells. Here, SRXN1 is linked to melanoma.