It is known that microRNAs(miRNAs)expression profile shows substantial changes in cells under DNA damage.Here,we did miRNA microarray and quantitative real-time PCR to comprehensively identify the differentially expressed miRNAs in colon cancer cell lines HCT116 p53/and HCT116 p53-/-.Cluster analysis revealed a panel of differentially expressed miRNAs which are regulated by p53and/or UV-C induced DNA damage.These altered miRNAs tend to be located in chromosomes 13,X and 17.Moreover,pathways enrichment analysis estimated that MAPK pathway,focal adheren pathway,p53 pathway and Wnt pathway were mediated by these miRNAs to exert their functions in DNA damage response.Additionally,we found that miR-320a,one of the UV-C induced miRNAs,play a role in protecting cells from DNA damage.Taken together,our results show that miRNAs are dynamic regulated in p53-dependent or-independent manners in different cell contexts and different situations following DNA damage. It is known that microRNAs (miRNAs) show profile shows substantial changes in cells under DNA damage. Here, we did miRNA microarray and quantitative real-time PCR to comprehensively identify the differentially expressed miRNAs in colon cancer cell lines HCT116 p53 / and HCT116 p53- /-Cluster analysis revealed a panel of differentially expressed miRNAs which are regulated by p53 and / or UV-C induced DNA damage. The altered miRNAs tend to be located in chromosomes 13, X and 17. More over, pathways enrichment analysis estimated that MAPK pathway , focal adheren pathway, p53 pathway and Wnt pathway were mediated by these miRNAs to exert their functions in DNA damage response. Additionally, we found that miR-320a, one of the UV-C induced miRNAs, play a role in protecting cells from DNA damage. Together, our results show that miRNAs are dynamically regulated in p53-dependent or-independent manners in different cell contexts and different situations following the DNA damage.