Keloid is a type of unusually raised scar. Botulinum toxin A (BTX‐A) has a great application potential in keloids treatment. Here, we investigated the functional role of BTX‐A in keloids. We separated keloid tissues and normal skin tissues from keloid patients and found that the expression of myofibroblast markers, α‐SMA, Collagen I, and Collagen III was increased in the keloid tissues as compared with normal skin tissues. Keloid fibroblasts derived from keloid tissues were treated with TGF‐β1 to induce the differentiation of fibroblasts into myofibroblasts. The keloid myofibroblasts displayed a significant up‐regulation of α‐SMA. BTX‐A enhanced the expression of adipocyte markers, PPARγ and C/EBPα, and increased the accumulation of lipid droplets, and reduced the expression of α‐SMA, Collagen I, and Collagen III in the keloid myofibroblasts. Moreover, BTX‐A enhanced the expression of BMP4 and p‐smad1/5/8. Noggin (BMP4 antagonist) treatment reversed BTX‐A‐mediated increase of PPARγ and C/EBPα expression and lipid droplets, and down‐regulation of α‐SMA, Collagen I, and Collagen III in primary keloid myofibroblasts. In conclusion, BTX‐A promoted the transdifferentiation of primary keloid myofibroblasts into adipocyte‐like cells, which may attribute to activate BMP4/Smad signalling pathway. Thus, this study provides new insights into the mechanism of BTX‐A in keloid. [ABSTRACT FROM AUTHOR]