Until now, Z-form RNAs were believed to only adopt a left-handed double-helix structure. In this study, we describe the first observation of a right-handed Z-form RNA in NMR solution formed by L-nucleic acid RNA and present the first resolution of structure of the complex between a right-handed Z-form RNA and a curaxin ligand. These results provide a platform for the design of topology specific to Z-form-targeting compounds and are valuable for the development of new potent anticancer drugs.