RNA, as one of the biomolecules with the most structural and functional diversity, is an attractive therapeutic target.(1) Employing combinatorial chemistry methods, small peptide ligands were found, which bind to a short RNA with important biological functions. A 23-nt RNA oligonucleotide from the cholesterol ester transfer protein mRNA was chosen as a molecular target.(2) A 27-nt RNA oligonucleotide from the human immunodeficiency virus type-1 (HIV-1) TAR RNA was used to control the binding specificity.(3) Tetrapeptide libraries, composed of the amino acids Lys, Tyr, Leu, Ile, and Arg, with and without C- and N-terminal lysines, were synthesized by a combination of combinatorial and divergent solid-phase synthesis. Gel-shift affinity screening was used to extract the peptides with the best RNA binding properties. The peptide Lys-Tyr-Lys-Leu-Tyr-Lys-Cys-NH(2) (1) showing micromolar affinity to its RNA target was characterized with circular dichroism (CD), ultra violet (UV) measurement, and (1)H NMR spectroscopy.