Objective: To study the expression and significance of squamous cell carcinoma antigen-1 (SCCA1) in keratinocytes from the lesion of cutaneous lupus erythematosus. Methods: The keratinocytes were isolated from the human skin and cultured in serum-free media. The total proteins of keratinocytes were separated by 2-dimensional gel electrophoresis. The differential proteins were analyzed using ImageMaster 2D analysis software after staining and identified by MALDI-TOF-MS. The expressional levels of the proteins were further confirmed by Western blot analysis. Results: We successfully in vitro cultured human skin primary keratinocytes and established 2-dimensional electrophoresis profiles with high resolution and reproducibility. The SCCA1 protein was up-regulated in the keratinocytes from lesion of CLE compared to the normal group,and the result from both proteomics approach agreed with that of Western blot analysis. Conclusion: The SCCA1 protein was up-regulated in the keratinocytes from lesion of CLE,which may be related to the development of CLE. However,the pathogenesis of over expression of SCCA1 need further study.