A physical stimuli, it has been reported that cyclic tensile strain can promote bone marrow-derived mesenchymal stem cells (BMSCs) to differentiate into cardiomyocytes, but the underlying mechanisms have been poorly elucidated so far. Here, we used a mimicking loading strain, cyclic biaxial tensile strain (CBTS), and found it can promote BMSCs to differentiate into cardiomyocytes. When the CBTS were loaded, the cells expressed cardiac-specific markers GATA4, TNNT2, MEF-2c, and Cx43, meanwhile we found miR-27a decreased and stem cell factor (SCF) increased. When we overexpressed miR-27a, the cardiac-specific markers were down-regulated; we got the same results when SCF was knocked down by siRNA. Interestingly, we found SCF is a potential target of miR-27a by a bioinformatic analysis. So, we overexpressed miR-27a, and found SCF decreased both in mRNA and protein level. And, When miR-27a was co-transfected with SCF-3'UTR, it significantly reduced the luciferase activity, but not when co-transfected with SCF-3'UTR mutation plasmid. Furthermore, after transfected both miR-27a and SCF siRNA, and the protein expression of the markers were more down-regulated than that of single of them. Taken together, we found CBTS can promote BMSCs to differentiate into cardiomyocytes, and miR-27a functions as a mechano-sensitive miRNA in this process by targeting SCF.Keywords: Bone marrow-derived mesenchymal stem cells; Cardiomyocyte-like cells; Cyclic biaxial tensile strain; Differentiation; Mechano-sensitive miRNA; Stem cell factor.