Herein, we report the first observation of Negative differential resistance (NDR) associated with resistance switching in Vanadyl-phthalocyanine (VOPc) based devices with the configuration: ITO/F4TCNQ/VOPc/MoO3/Al. It was observed that the devices were initially at low resistance ON state (LS) and were switched to high resistance OFF state (HS) at sufficient applied bias. The NDR behaviour was observed during the initial sweep for each device (often referred to as the writing process). The ON/OFF state transition was attributed to the formation and neutralization of interface dipoles at the ITO/VOPc interface. Finally, the observed non-volatile RS switching behaviour was demonstrated employing impedance spectroscopic studies. This study opens up the potential applications of VOPc Resistance Switching devices in security and data protection applications. © 2020 Elsevier B.V.