Objective To evaluate the effect and mechanism of microRNA-21 in hypertrophic scars （HS） formation and to provide novel target in biological control of HS. Methods Normal skin tissue and HS tissue were harvested. Collagen quantitative detection and histological observation were carried out. The expression of collagen 1A1 （Col1A1）, collagen 3A1 （Col3A1）, Fibronectin （FN） and α-SMA were detected by quantitative real-time PCR. The expression of microRNA-21 mRNA in normal skin tissue and HS tissue were also detected. Cells isolated from normal skin tissues and HS tissues were cultured, the microRNA-21 antisense RNA interference vector were constructed, while TGF-β was added at the same time. Furthermore, the effects of inhibitor-microRNA-21 and TGF-β on the biological characteristics of fibroblasts were observed. Results The content of collagen in hypertrophic scar was higher than that in normal skin. The expression of extracellular matrix such as Col1A1, Col3A1, FN and α-SMA in scar tissue were significantly increased. The expression of microRNA-21 in HS tissue was higher than in normal tissue. TGF-βenhanced the expression of microRNA-21 in fibroblasts of HS tissues, while the inhibition of microRNA-21 decreased the expression of those scar-related genes. Conclusion The skin after wound healing could increase the expression of microRNA-21 which promotes the synthesis of extracellular matrix, and TGF-βmay further strengthen the role of microRNA-21 in the formation of HS.