The G,2,/M arrest of human oral epithelial carcinoma KB cells could be induced by the synergistic effect of ionizing radiation with paclitaxel, which results in the formation of multinucleated giant cells and eventually cell death. Earlier biochip screening analysis found that ten genes related to regulate cell division have been differential expression after treated with ionizing radiation and/or paclitaxel. This study was to investigate the potential molecular mechanism by quantitative assessment two gene expression levels among the ten genes. The SPATA5L1 gene was quantified by real-time quantitative PCR. And the protein expression levels of Cyclin B2 and SPATA5L1 were detected by Western Blot. The results show that the expression of SPATA5L1 gene increase after different doses irradiation (below 6 Gy) or irradiation combined with 40 nmol/L paclitaxel, however, the expression of Cyclin B2 decrease at the same time. We suppose that the expression of up-regulated SPATA5L1 and down-regulated Cyclin B2 maybe play a crucial role in the G,2,/M arrest and the formation of multinucleated giant cells, which block the cytoplasm split to form new daughter cell after nucleolus division.