The primary human hypertrophic scar and normal skin fibroblasts were successfully established and identified by HSP47 and FSP markers. On the other hand, different pattern of protein expressions were found in cultured fibroblasts from hypertrophic scar and normal fibroblasts skin cells after treatment with the chitosan derivatives sheet. The CTCF protein was up-regulated in fibroblasts hypertrophic scar upon treatment with chitosan derivatives. In contrast, the amount of CTCF protein was found unchanged in normal skin fibroblasts both treated and untreated. The YB-1 protein was expressed almost similarly in normal and hypertrophic scar when treated with chitosan but the expression differed when untreated. The c-myc and p53 proteins were expressed in fibroblasts hypertrophic scar followed by up-regulation after chitosan derivatives treatment. The c-myc and p53 expressions were not detected in normal fibroblasts neither untreated nor treated. The CTCF, YB-1, c-myc and p53 proteins behaved in different manners in human hypertrophic scar and normal fibroblasts skin cells. The novel chitosan derivatives sheet in this study may play roles in the control of cell growth and proliferation of human hypertrophic scar and normal fibroblasts skin cells. The mechanisms underlying expression of these protein factors remain unclear and further studies are still undergoing in our laboratory.