Phthalocyanines　(Pc)　have　received　considerable　attention　in　the　design　of　photosensitizers　for　photodynamic　therapy　(PDT).　It　is　of　great　interest　to　design　novel　Pc-based　photosensitizer　with　improved　biological　efficiency,　which　largely　relies　on　the　understanding　of　the　interactions　of　Pc　with　cell　membranes　at　a　molecular　level.　Here,　via　all-atom　molecular　dynamics　simulations,　we　explored　the　interaction　mechanism　between　a　model　phospholipid　bilayer　and　three　zinc　Pc　(ZnPc)　molecules　with　different　hydrophobicity　in　nature.　We　find　that　the　adsorption　and　insertion　behaviors　of　ZnPc　molecules　in　the　model　bilayer　are　different　due　to　the　differing　hydrophobicity　and　interaction　patterns　with　phospholipids.　Moreover,　our　simulations　demonstrate　that　the　conjunction　of　a　ZnPc　skeleton　with　a　cholesterol　moiety　may　reduce　the　intrinsic　molecular　rotation　of　ZnPc　in　membranes,　presumably　leading　to　an　increase　of　the　generation　efficiency　of　reactive　oxygen　species　for　PDT.　The　molecular　insights　obtained　here　are　likely　to　help　improve　the　rational　design　of　novel　photosensitizers　with　enhanced　cellular　uptake　and　photocytotoxic　activity.