MicroRNAs are short, 18- to 25-nt sequences of noncoding, single-stranded RNA that function as regulatory molecules and participate in a series of vital processes including early development, cell proliferation, cell differentiation, apoptosis, substance metabolism and the pathogenesis of human diseases. This study compared the microRNA profiles of patients with systemic scleroderma (SSc) and healthy control individuals to investigate the pathogenesis of SSc. Skin tissue was isolated from three patients with SSc and three healthy controls. miRNA microarray chip analysis identified 24 miRNAs that were differentially expressed in patients with SSc and 6 microRNAs that may be correlated with the pathogenesis of SSc. The results of the microarray analysis were confirmed using real-time PCR. This work suggests that miRNAs may be potential diagnosis biomarkers and are likely to be involved in the pathogenesis of SSc.