The GB virus C/hepatitis G virus (GBV C/HGV) is a Flaviviridae member that despite its non pathogenicity, has become of great interest given that it could inhibit the replication of the human immunodeficiency virus (HIV). Therefore, a better knowledge of the virus peptides involved in the cellular membrane fusion mechanism has become our aim. The selected peptide, named E2(347-363), corresponds to the GBV-C/HGV E2 protein and has been synthesized in order to study its interaction with in vitro membrane models. Two phospholipids, varying the charge and the unsaturations of the hydrocarbon chain have been chosen: 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-dioleoyl-sn-glycero-3-[phospho-rac-(1-glycerol)] (sodium salt) (DOPG). For our porpoise, we have used the Langmuir monolayer technique and Brewster angle microscopy (BAM) to gain deeper insight into the peptide/lipid interactions. The results obtained allow us to argue in favour of considering E2(347-363) a success candidate for developing further experiments in order to determine its potential role in the GBV C/HGV virus/cell membrane fusion process.