Photodynamic　therapy　(PDT)　has　been　accepted　as　an　alternative　treatment　for　cancer.　The　rationale　for　the　development　of　PDT　for　cancer　is　that　target　specificity　can　be　achieved　by　controlling　the　location　at　which　light　activates　the　drug,　i.e.　photosensitiser.　Metal　phthalocyanines　represent　a　new　class　of　photosensitisers　developed　for　cancer　treatment.　In　the　present　study,　we　focused　on　exploring　molecular　mechanisms　of　the　lead　photosensitiser　PHOTOCYANINE　on　hepatocellular　carcinoma　(HCC)　HepG2　cells　to　guide　our　future　development　of　PHOTOCYANINE.　Growth　inhibition　potency　of　PHOTOCYANINE　and　its　analogues　was　tested　in　vitro　with　and　without　irradiation　at　wavelength　670　nm.　Irradiation　shifted　the　concentration-growth　inhibition　curves　of　PHOTOCYANINE　to　the　left　and　decreased　the　IC(50)s　of　PHOTOCYANINE　required　to　produce　equivalent　inhibition　by　200-fold　on　various　cell　lines.　The　amphipathic　PHOTOCYANINE　permeated　through　HepG2　cell　membrane　and　predominately　distributed　to　lysosome　and　mitochondria,　where　it　significantly　reduced　mitochondrial　membrane　potential　(Delta　Psi　m)　and　increased　caspase-3　activity　in　a　concentration-dependent　manner　after　irradiation.　Early　apoptosis　of　HepG2　occurred　followed　by　necrosis　when　concentrations　of　PHOTOCYANINE　were　increased　in　the　presence　of　irradiation.　Reactive　oxygen　species　(ROS)　production　was　significant　following　PHOTOCYANINE　plus　irradiation　treatment　and　cell　cycle　was　mainly　arrested　at　G(2)/M　stage.　In　conclusion,　PHOTOCYANINE,　once　irradiated,　induces　HepG2　cells　into　apoptosis　via　reducing　DWm,　producing　ROS,　activating　caspase-3,　and　causing　cell　arrest　at　G(2)/M　stage.　This　study　provides　important　insights　into　molecular　mechanisms　of　the　anti-cancer　PHOTOCYANINE,　which　now　is　being　applied　for　in　the　clinical　trials　II　in　China.　Published　by　Elsevier　Ltd.