To study the clinical significance of autoantibodies in Chinese patients with new-onset systemic lupus erythematosus (SLE), we enrolled 526 new-onset patients who met the 1997 Updated American College of Rheumatology SLE Classification Criteria for a retrospective cohort study. Chi-square test and Wilcoxon rank-sum test were used to detect the relationship of autoantibodies with clinical manifestations and serological results respectively. Our results demonstrated that the positive rate of anti-ribosomal P protein (anti-P) antibody in female patients was higher than that in male patients (41.2% vs. 22%,P= 0.008). Patients with anti-SSB (43.95 ± 73.12 vs. 40.92 ± 75.75,P= 0.004; 63.93 ± 103.56 vs. 55.06 ± 120.84,P= 0.008 respectively) antibodies had higher levels of alanine aminotransferase (ALT) and aspartate transaminase (AST), whereas those with anti-P antibody (28.90 ± 25.70 vs. 50.08 ± 93.00,P= 0.014; 38.51 ± 48.19 vs. 69.95 ± 142.67,P= 0.047, respectively) had lower levels of them. Anti-dsDNA antibody (P= 0.021) was associated with pulmonary arterial hypertension (PAH). The patients with anti-Ro60 (P= 0.044), anti-P (P= 0.012) and anti-dsDNA (P= 0.013) antibodies were less likely to develop Interstitial lung disease. Anti-SmRNP antibody was correlated to lower prevalence of neuropsychiatric symptoms (P= 0.037), and patients with anti-centromere antibody (ACA) were more likely to develop serositis (P= 0.016).We identified five clusters of SLE-related autoantibodies, confirmed previously reported associations of autoantibodies, and discovered new associations.