Circular RNAs (circRNAs) from back-splicing have been found in every cell and tissue. By binding to miRNAs and proteins or even by encoding small proteins, circRNAs are now emerging as important regulators in modulating transcription, RNA splicing and interference. The highlighted discovery reports an important role of circRNAs in antiviral innate immunity by binding PKR as PKR inhibitors. Rapid degradation of circRNAs by activated RNase L from virus infection or poly I:C stimulation is required to free PKR for its activation. Systemic lupus erythematosus patients remark with circRNA reduction and aberrant PKR activation.