Salt-inducible kinase 2 (SIK2) is a member of the AMP-activated serine/threonine kinase family. It has been reported that inhibition of SIK2 can enhance the cytotoxicity of paclitaxel, promote premitotic apoptosis, and lead to cell cycle arrest in the metaphase. Thus, targeting SIK2 may be a therapeutic strategy for cancers drug and radiotherapy resistance. Mitotic catastrophe is a type of abnormal mitosis leading to cell death characterized by the multipolar spindle and multinucleation, which was first discovered during an ionizing radiation (IR) -induced cell damage. However, the mechanism of mitotic catastrophe is not well understood. The present study aimed to assess the effect of the knockdown of SIK2 on IR-induced mitotic catastrophe.