Abstract Objective: At present, human bone marrow mesenchymal stem cells (hBMSCs) used as target vectors for hypopharyngeal cancer is a new therapeutic direction of great potential. However, hBMSCs would be transmitted into cancer-associated fibroblasts(CAFs) under the induction of hypopharyngeal cancer. Here, we aimed to determine whether microRNA-21(miR-21) in exosomes from FaDu cells would play a role in hypopharyngeal cancer induced transition of hBMSCs to CAFs. Methods: qRT-PCR and western blot were employed to investigate expression level of miR-21 in hypopharyngeal cancer patient samples and FaDu cells. The exosomes were collected from FaDu cells then isolated and identified. Cell morphological changes were observed by inverted phase contrast microscope. Expression level of CAF-related proteins, includingα-SMA and FAP, were assessed by qRT-PCR and western blot. Cell cycle of hBMSCs were determined by flow cytometry. Results: MiR-21 expression level was up-regulated in hypopharyngeal cancer tissue and FaDu cells. Exosomes from FaDu cells promoted CAFs-like features of hBMSCs, including up-regulation of α-SMA and FAP and cell morphological changes. Proportions of hMBSCs in G1 phase significantly decreased, while proportions of hMBSCs in G2 phase significantly decreased at the presence of exosomes from FaDu cells. What’s more, miR-21 knock-out in FaDu cells suppressed transition of bone marrow mesenchymal stem cells to cancer-associated fibroblasts and reversed the cell cycle change. Conclusions: Our data showed that miR-21 promotes hypopharyngeal cancer induced transition of bone marrow mesenchymal stem cells to cancer-associated fibroblasts. Keywords: Hypopharyngeal cancer, Bone marrow mesenchymal stem cells, Cancer-associated fibroblasts, MicroRNA-21, Exosomes