It has been known that genome instability exists in many cancers,and it may be a potential cause of tumorigenesis.Our studies demonstrated that genomic instability can be induced by ionizing radiation in human hepatocytes,and CDT1、RAN、HAVCR2 genes were differential expressed in human hepatocytes that were genomic instability induced by ionizing radiation.To further investigate the regulatory effects of CDT1、RAN、HAVCR2 genes on genomic instability induced by ionizing radiation,RNA interference was used to silence the genes including CDT1、RAN respectively in human hepatocytes that were genomic instability.Meanwhile,CDT1 and RAN were overexpressed respectively.The apoptosis was detected by Annexin Ⅴ-APC flow cytometry(FCM) and the cell cycle was determined by FCM with single PI staining.And the expression changes of CDT1、RAN、HAVCR2、p53 genes were assayed by real time fluorescence quantitative PCR technology.The results showed that CDT1 silencing downregulated RAN expression,upregulated HAVCR2、p53 genes expression,and inhibited apoptosis; however,overexpression of CDT1 downregulated RAN、p53 genes and promotes apoptosis.RAN silencing upregulated HAVCR2、p53 genes expression and inhibited apoptosis,arrest the cells at G1 phase; however,overexpression of RAN downregulated CDT1、p53 genes and promotes apoptosis.In conclusion,CDT1、RAN、HAVCR2 、p53 genes interacted each other,involving genomic instability through apoptosis regulation and cell cycle regulation.