AIM: To study the suppressive effect of glycogen synthase kinase-3β( GSK-3β) knockdown by RNA interference on the formation of keloid .METHODS:Human keloid fibroblasts ( KFB) in vitro were transfected with 3 pairs of specific GSK-3βsmall interfering RNA (siRNA).The best siRNA to inhibit the GSK-3βexpression in human KFB was screen by RT-PCR and Western blot .The expression of GSK-3βand related proteins at mRNA and protein levels in the KFB was determined by RT-PCR and Western blot .RESULTS: The GSK-3βsiRNA1434 remarkably inhibited the expression of GSK-3βat mRNA and proteins levels in the human KFB .After transfection with GSK-3βsiRNA, the protein levels of β-catenin, p-GSK-3β, Wnt2 and cyclin D1 were all decreased.KFB growth became slow.With the extension of time, the inhibition of cell growth increased , and the cell doubling time was significantly delayed .CONCLUSION:siRNA targeting GSK-3βefficiently knocks down the expression of GSK-3βin the human KFB, and inhibits the activation of Wnt signaling pathway , thus inhibiting the growth of keloid .GSK-3βmay be a potential therapeutic target for keloid .