Transferrin in insects is known as an iron transporter, an antibiotic agent, a vitellogenin, and a juvenile hormone-regulated protein. We show here a novel functional role for insect transferrin. Stresses, such as iron overload, bacterial or fungal challenge, cold or heat shock, wounding, and H2O2 or paraquat exposure, cause upregulation of the beetle Apriona germari transferrin (AgTf) gene in the fat body and epidermis, and they cause increased AgTf protein levels. RNA interference (RNAi)-mediated AgTf reduction results in rapid induction of apoptotic cell death in the fat body during exposure to heat stress. The observed effect of AgTf RNAi indicates that AgTf inhibits heat stress-induced apoptotic cell death, suggesting a functional role for AgTf in defense and stress responses in the beetle.