Abstract:CRISPR-Cas system has been recognized as an adaptive immune system in bacteria and archaea recently. Using this system, prokaryote could target and degrade invading nucleic acids effectively. During this process, a novel kind of non-coding RNA–crRNA is generated and required by guiding multiple Cas proteins working together to capture and eliminate foreign DNA or RNA. Based on achievements in recent years, we review the mechanism of crRNA biogenesis and interference, and propose the future research interests in this field.