Significance G-quadruplexes (G4) are four-stranded nucleic acid structures implicated in important biological processes. Interaction between G4 and proteins is essential for the cellular functions of G4. The DEAH (Asp-Glu-Ala-His) box RNA helicase associated with AU-rich element (RHAU) (also named DHX36 or G4R1) specifically binds and unwinds G4 structures. The structure of an 18-aa peptide, identified as the G4-binding domain of RHAU, was solved in the complex with a G4 by NMR spectroscopy. The structure of the complex explains how RHAU specifically recognizes G4 structures and suggests a strategy for G4 recognition by proteins.