Objective To investigate the effect of shikonin on the collagen deposition of human hypertro⁃ phic scar fibroblasts from the perspective of PTEN. Methods Hematoxylin ⁃ eosin staining and Masson staining were used to identify hypertrophic scar tissue. Immunofluorescence was used to identify fibroblasts. The relative expression level of PTEN was detected by Western blot at the tissue level. Hypertrophic scar fibroblasts were ran⁃ domly divided into dimethyl sulfone group，shikonin group，control group，si ⁃NC group，shikonin+ si ⁃NC group and shikonin+si⁃PTENC group，western blot were used to detect the expression of PTEN and collagen⁃related proteins（Col1，Col3 and α⁃SMA）at protein levels，respectively. Results Compared with normal skin，PTEN was lower expressed in hypertrophic scar（P < 0.05）. shikonin was dissolved in dimethyl sulfone to make drug solution at IC50 concentration（13.46 μmol/L），which was used for human hypertrophic scar fibroblasts cell culture for 24 hours，shikonin down⁃regulated the expression levels of Col1，Col3 and α⁃SMA in human hypertrophic scar fibro⁃ blasts，while up⁃regulated the expression of PTEN（P < 0.05）. Transfected with si⁃PTEN，the expressions of Col1， Col3 and α⁃SMA in human hypertrophic scar fibroblasts were increased compared with the si⁃NC group（P < 0.05）. After co⁃transfection with shikonin + si⁃PTEN，the expressions of Col1，Col3 and α⁃SMA in human hypertrophic scar fibroblasts were increased compared with shikonin + si⁃NC group（P < 0.05）. Conclusion Shikonin can inhibit collagen deposition in hypertrophic scar fibroblasts by up⁃regulating PTEN expression.