Objective To investigate the effect and targeting of iRGD-exosomes-doxorubicin (iRGD-exo-dox) on the inhibition of A375 cell line. Methods The exosomes were extracted from the iRGD-transfected A375 cells. The doxorubicin was wrapped by electroporation. Flow cytometry was used to detect the affinity of iRGD-exo-dox to A375 cells. The ability of iRGD-exo-dox on inhibiting the proliferation of A375 cells was analyzed. Results The affinity of iRGD-exo-dox to A375 cells was higher than the blank-exo-dox. The proliferation of A375 cells was obviously inhibited by iRGD-exo-dox. The inhibition effect was not observed in blank-exo-dox group. Conclusion iRGD-exo-dox can inhibit the proliferation of A375 cells by targeting function.