The aim of this study was to characterize the molecular interactions zone between the plerocercoid of Ligula intestinalis and its host, a common bream Abramis brama. Using HPLC-MS/MS we performed a comparative proteomic analysis of washes from the parasite surface and from the body cavity of infected and uninfected fish. We identified both parasitic and host proteins on the helminth surface, reflecting an active molecular crosstalk. Functional analysis revealed cestode-specific metabolic and signaling pathways (eg. such as proline biosynthesis and TOR signaling), including those for amino acid biosynthesis, lipid transport, and nutrient sensing. Within the body cavity of infected fish, we detected parasite-derived proteins such as immunomodulators, proteases, and metabolic enzymes. Quantitative changes in host wash proteomes indicated activation of humoral immunity alongside remodeling of proteolytic regulation. Collectively, these data reveal the molecular foundation of L. intestinalis adaptation and the dynamic host-parasite relationships in this system.