To assess the presence of autoantibodies against epitopes of heterogenous nuclear ribonucleoprotein-Ⅰ (hnRNP-Ⅰ ) in systematic sclerosis (SSc) and to analyze their clinical significance, polypeptides of hnRNP-Ⅰ were designed by biological technical software and analyzed with both the Wonderful Biology Information System and DNA Star-Protean Analysis Software at the same time. In these ways, two polypeptides of hnRNP-Ⅰ were obtained based on their amino acid sequences, folding features, hydrophilic, curl style, dough kneading sensation and the possibility on the surface of proteins. They are named as hnRNP-Ⅰ-1 (NVKYNNDKSRDYTRPDLPSGDSQPSLDQT, 264-292 aa) and hnRNP-Ⅰ-2(QLP4REGQEDQGLTKDYGNSOL, 441-461 aa), simply designated as Ⅰ-1 and Ⅰ-2. The autoantibodies against hnRNPs were detected by means of ELISA using the synthetic epitopes polypeptides as antigen. It was found that the positive rate of detection for anti-Ⅰ-1 and anti-Ⅰ-2 autoantibodies were rather higher in SSc patients than that in other CTDs and the sensitivities and specificities of the testing with ELISA for anti-Ⅰ-1 and anti-Ⅰ-2 antibodies in SSc patients were 47.62%/93.43% and 38.1%/91.08%, without any significant difference between these two groups of testings. Also, there was no significant difference in the clinical features and laboratory findings, such as age, involvements in digestive and respiratory tracts and erythrocyte sedimentation rate etc., between the anti-Ⅰ-1-positive and -negative groups in SSc patients. However, the hnRNP-Ⅰ-autoantibody-positive group of patients had obviously shorter duration of disease course compared with that of the autoantibody-negative group. Anti-Ⅰ-1and anti-Ⅰ-2 autoantibodies also had no association with antinuclear antibody, anti-Sc170 and anti-centromere antibody (ACA) in SSc patients. So, it is apparent that the autoantibodies related with SSc may act through different pathways in the pathogenesis of SSc, and the hnRNP-Ⅰ autoantibody is a new type antibody occuring during the early stage of disease and appearing to have diagnostic and prognostic significances.