[Abstract] Objective: To investigate the effect of miR-616-3p on complement system attack on bone marrow mesenchymal stem cells (BMSCs) and its mechanism. Methods: The primary BMSCs were isolated from the marrow cavity of SD rats and transfected with miR-616-3p inhibitor. Then rBMSCs were intervened with the isolated allogeneic rat serum (ARS). The expression of miR-616-3p in rBMSCs was detected by qRT-PCR assay; The expression of membrane complement regulatory protein CD46 and apoptosis protein cleaved Caspase-3 were detected by using Western Blot; The proliferation activity was detected by MTT assay; Flow cytometry was used to detect the apoptosis rate and deposition of membrane attact complex (MAC) of rBMSCs. Then the relationship between miR-616-3p and CD46 was verified by dual luciferase report system. Results: ARS intervention could significantly promote the expression of miR-616-3p (P<0.05), inhibit the expression of CD46 protein (P<0.05), and then decrease the cell proliferation, promote the apoptosis rate and MAC deposition (P<0.05); After miR-616-3p inhibitor transfection, the expression of miR-616-3p decreased significantly in rBMSCs; Inhibition of miR-616-3p expression could promote the survival of rBMSCs and the expression of CD46 protein, inhibit the apoptosis and reduce the deposition of MAC in the rBMSCs intervented with ARS. Dual Luciferase Report System confirmed that CD46 was the target gene of miR-616-3p. Conclusion: Down-regulation of miR-616-3p can promote BMSCs proliferation, inhibit cell apoptosis and suppress the attack of complement system on rBMSCs by targeting CD46 expression.