Significance Metastasis is responsible for most of cancer-related deaths, which requires dramatic remodeling of the cytoskeleton. Circular RNA ASH2 (circASH2) functions as a powerful tumor suppressor via directly modulating stability of microfilament. The matchmaker function of circASH2 in delivering Tropomyosin 4 (TPM4) transcripts to the Y-box binding protein 1 (YBX1)/heterogeneous nuclear ribonucleoproteins (hnRNP) complex and then accelerating nonsense-mediated messenger RNA decay (NMD) of TPM4 is unexpected but should have a significant impact on our understanding of posttranscriptional regulation mediated by noncoding RNA (ncRNA). This study has provided convincing data on how a circular RNA (circRNA) regulates RNA-binding protein (RBP)’s function in a liquid–liquid phase separation (LLPS)-dependent manner, which represents a significant conceptual advancement in circRNA and RBP-related research.