Parasitic weed Phelipanche aegyptiaca, is an obligate plant parasite which causes severe damage to host crops. Agriculture crops mainly belong to Brassicaceae, Leguminosae, Cruciferae and Solanaceae plant families affected by this parasitic weed which leads to devastating loss to crops yield and economic growth. This root specific parasitic plant is not able to complete its life-cycle without a suitable host and is totally dependent on the host plant for organic nutrients. Therefore, flow of organic solute molecules towards parasites is essential for the survival of the parasitic weed and disturbance in this network modulated host-parasitic interaction, which induces resistance in host against these parasitic weeds. To develop host resistance to this parasitic weed, we silenced selected prominent genes associated with P. aegyptiaca using virus-induced gene silencing (VIGS) methods. Our results demonstrated that the total number of parasite tubercle attached to root of the host plant Nicotiana benthamiana significantly reduced upon silencing of P. aegyptiaca specific gene which encodes mannitol transporter, however silencing of other gene(s), have no significant effects. Thus, our study indicates that mannitol transport plays an important role in host-parasite interaction and silencing of this gene causes development of host resistance against this parasite.