The objective of this study was to investigate the expression and relationship of LL-37, plasmacytoid dendritic cells (pDCs) and interferon-alpha (IFN-α) in skin in systemic lupus erythematosus (SLE), and their role in SLE pathogenesis. Skin biopsies were taken from nine SLE patients and six healthy volunteers. Expression of LL-37, pDCs and IFN-α in skin specimens and consecutive sections of skin was detected with an immunohistochemical technique (IH); the expression of LL-37 and pDCs in the samples was detected with in situ hybridization (ISH). The expression levels of LL-37, pDCs and IFN-α were significantly higher in SLE skin than in that of healthy controls (p < 0.001) with either the IH or the ISH technique, and the location of positive expression in consecutive sections was similar. Correlation analysis showed that the expression levels of LL-37, pDCs and IFN-α correlated positively with each other. In conclusion, the expression of LL-37, pDCs and IFN-α was increased in the skin of patients with active SLE. It is necessary to study further the role of LL-37 in the pathogenesis of SLE, and the exact relationship among LL-37, pDCs and IFN-α.