Photodynamic therapy (PDT) is a novel therapeutic approach for combating various cancers. PDT involves the administration of a photosensitizer which generates singlet oxygen after light activation. FosPegⓇ is the liposomal formulation of mTHPC. In this in vitro study, the photodynamic efficacy of FosPegⓇ on a human colon cancer cell line (HT29) was investigated via studying the cellular uptake of FosPegⓇ, FosPegⓇ PDT mediated photocytotoxicity and the cell death mechanism were triggered. FosPegⓇ PDT demonstrated its antitumor effect in a drug and light dose-dependent manner in HT-29 cells. Lethal dose (LD50) was achieved with 0.4 μg/mL of drug and 3 J/cm-2 of light dose. FosPegⓇ PDT triggered apoptotic cell death via activating caspase cascade and regulating cell cycle progression. In conclusion, FosPegⓇ-PDT is an effective measure to combat human colon cancer cells.