Objective To investigate the effects of microRNA-17-92 on radiosensitivity of human mantle cell lymphoma cells. Methods Tetracycline-regulated pRevTet-On expression system was established to generate cell line Z138c-miR-17-92 with over-expressed miR-17-92 and cell line Z138c-TMP2. Cell proliferation was measured by 3 H-TdR incorporation and viable cell counting stained with typan blue. Cell cycle distribution was analysed by flow cytometry(FCM). Results More viable and proliferous cells were counted in group miR-17-92,when exposure dose was greater than 2 Gy and incubation time was longer than 48 h under the same condition (t = -3. 12 and -3.28,P ＜0. 05). The percentage of G2/M cells in group TMP2 was increased while no obvious cell cycle arrests were found in group miR-17-92 at 2 and 4 Gy (t = 2. 885, P ＜ 0.05 ). When cells were incubated for 96 h, higher percentage of propidium iodide (PI) positively stained cells were found in group TMP2 (24. 02% vs. 36. 16% )compared with group miR-17-92 (6.49% vs. 11.39% ) at 2 and 4 Gy, respectively( t = - 17.59, - 4. 972, P ＜ 0.05 ).Conclusions Overexpression of microRNA-17-92 decreased the radiosensitivity of human mantle cell lymphoma cells by inhibition of cell cycle changes and cell apoptosis.