Resonance Raman and surface-enhanced Raman spectroscopy were employed to study the interaction of hypericin with human serum albumin. The identification of the binding place for hypericin as well as the model for albumin-hypericin complex are presented. In this model hypericin interacts with tryptophan placed in II A subdomain of albumin. This interaction reflects (i) a change of the hydrophobicity of the tryptophan environment, (ii) the formation of an H-bond between the carbonyl group of hypericin and N1-H group of tryptophan, leading to a protonated-like carbonyl in the drug, (iii) a decrease of the strength of H bonding at the N1-H site of tryptophan, and (iv) a change of the tryptophan side-chain conformation.