Midbody is a transient structure assembled in the last step of mitosis and is currently conceptualized as a structural remnant subject to degradation following cytokinesis. However, our findings indicate that midbody regulation is more complicated than original thought. Knockdown spliceosome proteins in cells showed a multinuclear phenotype and abnormal midbody. Spliceosome and ribosome components are enriched in midbody. We further found that mRNA splicing and protein translation occurs in the midbody during last step of mitosis, which are necessary events for proper abscission of nascent daughter cells. Midbody spliced and translated PRC1 and NINL are essential for proper midbody function. Either PRC1 or NINL knockdown also showed a multinuclear phenotype and abnormal midbody. Treating cancer cells with both chemotherapy and spliceosome inhibitors dramatically lowers the concentration of both drugs, avoiding more severe side effects. Our study discovers a novel regulating mechanism for mitosis and provides a new strategy for cancer therapy.