Abstract: Microfilament is a multi-functional sub-cell structure, and it is also a sensor for ionizing radiation. In order to clarify the regulatory effect of long non-coding RNAs(lncRNA) in the alteration of microfilament dynamics caused by ionizing radiation, Swinholide A was used to depolymerize the microfilament and then, the lncRNA chip was used to detect the differentially expressed lncRNAs. Microfilament staining and network/structure analysis were used to evaluate the changes in microfilament skeleton. It was found that the expression of lncRNA XR_923426 was decreased after the microfilament depolymerization. Meanwhile, the overexpression of lncRNA XR_923426 could significantly alleviate the microfilament depolymerization caused by ionizing radiation. This provides a new clue for the research on the regulatory relationship between lncRNA targeted microfilament dynamics and radiation induced tumor death or metastasis, which is expected to develop into a new target for tumor treatment or normal tissue protection.