Abstract: Objective To investigate the expression levels of lncRNA Hotair, XIST, HI9 and MALATI in serum-derived exosomes of the patients with rheumatoid arthritis, and analyze their correlation with inflammatory parameters to explore the clinical diagnostic value for RA. Methods A total of 70 RA patients were collcted as the disease group , 40 patients with systemic lupus erythematosus ( SLE) during the same period as the disease control group, and 40 healthy people who undenvent physical examination as the healthy contol group. Their serum samples were collected and the exosomes were extracted from patients' serum. The concentration of exosomes was detected by nano particle diameter tracking instrument. The expression levels of lncRNA Hotair, XIST, HI9 and MALATI in serum-de-rived exosomes of each group were detected by RT-qPCR. Spearman correlation analysis was used to further analyze the correlation between the levels of Hotair, XIST and ESR, CRP, DAS-28 score of RA patients. The clinical diagnostic value of Hotair, XIST for RA were analyzed by ROC curve. Results Compared with the healthy control group, the concentration of serum-derived exosomes in RA patients was significantly higher than that in healthy control group ( P<0.05)，but there was no significant difference between RA group and SLE group ( P>0.05). Moreover, no obvious differences of the expression levels of IncRNA HI9 and MALATI were found among the three groups ( P>0.05). The expression levels of lncRNA Hotair and XIST in RA group were significantly higher than those in SLE group and HC control group ( P<0.001 ). The expression levels of lncRNA Hotair and XIST were positively correlated with ESR, CRP and DAS-28 score in RA patients (P<0.05). The AUCROC of serum-derived exosomes IncRNA Hotair, XIST in diagnosing RA were 0.84(95%CI= 0.78 to 0.90, P<0.001) and 0.76( 95%CI=0.68 to 0.83, P<0.001 ). Conclusion The expression levels of serum-de-rived exosomes lncRNA Hotair and XIST were significantly increased in RA patients, which was positively correlated with ESR, CRP and Das-28. These results suggested that serum-derived exosomes lncRNA Hotair and Xist may be used as potential biomarkers for RA diagnosis.