Persistent organic compounds, particularly those of industrial origin, are highly toxic, bioaccumulative, persistent, and capable of traveling long distances. The World Health Organization even considers some of them potential carcinogens. In the marine environment, polychlorinated biphenyls (PCBs) accumulate in sediments, leading to continuous exposure and potentially causing adverse effects on ecosystems and food chains. In particular, concentrations of seven key PCBs (IUPAC numbers 28, 52, 101, 118, 138, 153 and 180) are usually closely monitored. Despite advances in understanding the metabolic processes of PCBs, their absorption and diffusion mechanisms across cell membranes remain insufficiently understood. These membranes act as reservoirs for PCBs, prolonging chronic exposure. In this study, we investigate the permeation process of these compounds across lipid membranes by means of classical molecular dynamics (CMD) in combination with the umbrella sampling approach, using a model composed of 128 1,2-dioleoyl-sn-glycero-3-phosphocholine lipids (DOPC). The free energy profile shows the penetration process is largely favoured thermodynamically, with a progressively decrease of the energy until reaching the energy minima close to the centre of the membrane. The analysis of key regions along the diffusion pathway is particularly relevant for studying intermolecular interactions between PCBs and lipid bilayers. Therefore, the characterization of contaminant-membrane interactions was initially conducted using a combination of quantum mechanics/molecular mechanics (QM/MM) calculations and energy decomposition analysis (EDA). This approach provides deeper insight into the underlying mechanisms, including the contributions of electrostatic, exchange, repulsion, and polarization interactions, which together elucidate the permeation process.