Cytochrome c (cyt c) is a mitochondrial membrane hemoprotein of high physiological importance. Fisrt, cyt c is one of the key elements of respiration chain transferring electrons from cyt c reductase (bc1 complex) to cyt c oxidase. Second, release of cyt c from the intermembrane space of mitochondria into the cytosol triggers the apoptotic pathway. The idea that specific interactions between cyt c and cardiolipin (CL), the main lipid component of mitochondrial membrane, are crucial to the protein biological activities, constantly receives further corroboration from both theoretical and experimental studies. Despite considerable progress achieved in the field of cyt c – CL biophysics, the detailed structural description of protein-lipid complexation is still lacking. In the present study we applied Förster resonance energy transfer (RET) technique to give comprehensive characterization of cyt c binding to the model lipid membranes composed of the mixtures of zwitterionic lipid phosphatidylcholine (PC) with anionic lipids phosphatidylglycerol (PG), phosphatidylserine (PS) or cardiolipin (CL) in different molar ratios. The donor-acceptor pairs were represented by either anthrylvinyl-labeled PC (AV-PC) or anthrylvinyl-labeled CL (AV-CL) incorporated in trace amounts in lipid vesicles, and heme moiety of cyt c. Association of the protein with the lipid bilayers led to the decrease in donor fluorescence reflecting energy transfer from AV fluorophore to heme. The most effective RET was found for CL-containing membranes. This observation has been interpreted in terms of higher affinity of cyt c to CL as compared to other anionic lipids. In order to get understanding of protein specificity to CL, RET was measured as a function of CL content and ionic strength. Monte Carlo analysis of multiple datasets revealed a complex interplay between several processes, namely i) lipid demixing; ii) CL transition into extended conformation; iii) formation of hexagonal phase. The switch between these states was found to be controlled by CL content and salt concentration. These characteristics of cyt c – CL interaction are of great interest not only in the context of regulating cyt c electron transfer and apoptotic propensities, but also from the viewpoint of the protein biogenesis.