MicroRNAs (miRNAs or miRs) play important roles in numerous cellular processes, including development, proliferation, tumorigenesis and apoptosis. It has been reported that miRNA expression is induced by ionizing radiation (IR) in cancer cells. However, the underlying molecular mechanisms are not yet fully understood. In this study, endogenous miR320a and its primary precursor (primiR320a) were assayed by reverse transcriptionquantitative PCR (RTqPCR). Luciferase activities were measured using a dualluciferase reporter assay system. Western blot analysis was used to determine the protein expressions of upstream and downstream genes of miR320a. Cell apoptosis was evaluated by Annexin V apoptosis assay and cell proliferation was measured using the trypan blue exclusion method. The results revealed that miR320a expression increased linearly with the IR dose and treatment duration. Three transcription factors, activating transcription factor 2 (ATF2), ETS transcription factor (ELK1) and YY1 transcription factor (YY1), were activated by p38 mitogenactivated protein kinase (MAPK) and mitogenactivated protein kinase 8 (JNK) and by upregulated miR320a expression under IR conditions. In addition, it was identified that Xlinked inhibitor of apoptosis (XIAP) was an miR320a target gene during the IR response. By targeting XIAP, miR320a induced apoptosis and inhibited the proliferation of the cancer cells. On the whole, the results of this study demonstrated that miRNA320a, regulated by the p38 MAPK/JNK pathway, enhanced the radiosensitivity of cancer cells by inhibiting XIAP and this may thus prove to be a potential therapeutic approach with which to overcome radioresistance in cancer treatment.