Objective：To investigate the role of growth differentiation factor 15（GDF15）in irradiation resistance of human bone marrow mesenchymal stem cells（BM-MSCs）and determine its underlying mechanism. Methods：The BM-MSCs were transfected with GDF15 siRNA using Lipofectamine 3000. After the irradiation of BM-MSCs with 9 Gy Co-60 γ-rays，the cell cycle and apoptosis were detected by flow cytometry，CCK-8 was used to detect cell proliferation，and JC-1 was used to detect mitochondrial membrane potential，immunofluorescence，quantitative real-time PCR（RT-qPCR）and Western blot were used to detect the expression of GDF15，and the key molecules in ERK/Bcl-2 signaling pathway. Results：After irradiation，the expression of GDF15 was increased significantly. Interference of GDF15 had no significant effect on cell cycle，proliferation and apoptosis in no-irradiated BM-MSCs（P - 0.05）. Interference of GDF15 in BM-MSCs suffering form irradiation increased G2 phase arrest（P - 0.05），inhibited cell proliferation significantly（P - 0.01），and decreased mitochondrial membrane potential. Meanwhile，Caspase3 was activated and apoptosis was significantly increased（P - 0.05）. The phosphorylation level of ERK1/2 and the expression level of Bcl-2 in GDF15 interference cells decreased significantly，while the expression of Bax increased significantly. Conclusion：The up-regulated expression of GDF15-induces upon irradiation，and enhances irradiation resistance of BM-MSCs through the activation of ERK/Bcl-2 signaling pathway.