Using Raman spectroscopy, we studied and compared the characteristics of microcosmic and photosensitive damage of the liposomes of mixed DPPE and DPPC sensitized by hypocrellin and its derivatives at the molecular level. After photosensitive damage, the structure of the liposomes of mixed phospholipids changed considerably. The trans conformation decreased and gauche conformation increased. The longitudinal order parameter in chains and the lateral order parameter between chains decreased clearly. The results suggested that the hydrocarbon chains of DPPE and DPPC were broken after the photodamage sensitized by hypocrellin B (HB) and 5-Br-hypocrellin B (5-Br-HB). Photosensitive damage on the liposomes sensitized by 5-Br-HB is stronger than that by hypocrellin A (HA) and HB, that is, 5-Br-HB > HB > HA. The results elucidated the sites of interaction or binding to HA, HB and 5-Br-HB in the liposomes and these changed with the use of drugs.