Zinc(II)-phthalocyanine　(ZnPc)　is　a　metal　photosensitizer.　In　the　present　study,　we　formulated　the　poorly-soluble　ZnPc　in　Cremophor　EL　solution　to　enhance　its　solubility　and　determined　its　intracellular　distribution　and　mechanisms　of　action　on　human　hepatocellular　carcinoma　HepG2　cells.　ZnPc　uptake　by　the　cells　reached　a　plateau　by　8　h.　ZnPc　primarily　located　in　mitochondria,　lysosome　and　endoplasmic　reticulum.　The　concentration-growth　inhibition　curves　of　ZnPc　on　the　cell　lines　were　pharmacodynamically　enhanced　by　10-50　folds　by　irradiation.　Once　irradiated,　ZnPc　produced　significant　amount　of　reactive　oxygen　species　(ROS),　activated　caspase-3　and　caspase-9,　arrested　cell　cycle　mainly　at　G2/M　stage,　and　decreased　membrane　potential　(Delta　Psi　m)　of　HepG2　cells.　In　conclusion,　the　present　study　first　elucidated　cellular　and　molecular　mechanisms　of　ZnPc　on　HepG2　cells.　(C)　2012　Elsevier　Ireland　Ltd.　All　rights　reserved.