Background: Exosomes play important roles in intercellular communication by delivering microRNAs (miRNAs) that mediate tumor initiation and development, including those in diffuse large B cell lymphoma (DLBCL). To date, however, limited studies on the inhibitory effect of exosomes derived from human bone marrow-derived mesenchymal stem cells (hBMSCs) on DLBCL progression have been reported. Therefore, this study aimed to investigate the role of hBMSC-secreted exosomes carrying microRNA-124-3p in the development of DLBCL.Methods: Microarray-based expression analysis was adopted to identify differentially expressed genes and regulatory miRNAs, which revealed the candidate NFATc1. Next, the binding affinity between miR-124-3p and NFATc1 was using luciferase activity assays. The mechanism underlying NFATc1 regulation was investigated using lentiviral transfections. Subsequently, DLBCL cells were cocultured with exosomes derived from hBMSCs transfected with a miR-124-3p mimic or control. Proliferation and apoptosis were measured in vitro. Finally, the effects of hBMSC-derived miR-124-3p on tumor growth were investigated in vivo.Results: MiR-124-3p was downregulated while NFATc1 was upregulated in DLBCL cells. MiR-124-3p specifically targeted and negatively regulated the expression of NFATc1 in DLBCL cells, upregulated miR-124-3p-inhibited DLBCL cell proliferation and promoted apoptosis. In addition, we found that hBMSC-derived exosomes carrying miR-124-3p repressed DLBCL cell proliferation both in vitro and in vivo.Conclusion: hBMSC-derived exosomal miR-124-3p represses the development of DLBCL through the downregulation of NFATc1.