A definitive interaction between the mitochondria signature phospholipid- Cardiolipin (CL) and the anti-cancer compound- Curcumin (CUR), was subjected as part of a model membrane system of the mitochondria membranes. A small unilamellar and giant lipid vesicles mimicking mitochondria membrane bilayer were employed to address biophysical aspects of interaction between CUR and CL. We showed that CUR exhibit enhancement of fluorescence corresponding to increasing amounts of CL, indicating a preferential interaction between them. The different biophysical methods that were applied on this system, explains the singular affinity of CUR to CL. Furthermore, to some extend the ability of CUR to alter broad spectrum of metabolic processes. The investigation of this artificial membrane system along with the inquiry of CUR influences may yield information about the role of mitochondria membranes in cancer and can suggest CUR as an anticancer future therapy