Objective: To investigate the expression level of miR-342-3p in peripheral blood mononuclear cells (PBMCs) of patients with rheumatoid arthritis (RA) and its effect on inflammatory response and migration of synovial fibroblasts in RA (RA-FLS)., Methods: PBMCs were collected from 30 healthy individuals and 50 RA patients for detecting the expression of miR-342-3p, and its correlation with the clinical indicators RF, ESR, anti-CCP, hs-CRP, C3, DAS-28, SAS, and SDS was analyzed. In RA-FLS cultures, the effect of transfection of miR-342-3p mimics and inhibitor on TNF- α -induced inflammatory response of the cells was evaluated by detecting the expressions of IL-1β, IL-6, IL-10, and TNF- α using ELISA. CCK8 assay and Transwell assay were used for detecting the changes in cell viability and migration ability of the synovial cells., Results: In RA patients, the expression level of miR-342-3p was significantly lowered in the PBMCs ( P < 0.05) with an area under the ROC curve of 97.53% and showed inverse correlations with RF ( r =-0.321), ESR( r =-0.284), anti-CCP ( r =-0.355), hs-CRP ( r =-0.320), C3 ( r =-0.294), DAS-28 ( r =-0.395), SAS ( r =-0.366), and SDS ( r =-0.397) (all P < 0.05); a low expression of miR-342-3p was strongly associated with elevated levels of anti-CCP, DAS-28, SDS, and SAS (all with a rule support greater than 85%, confidence greater than 88%, and lift greater than 1). In cultured RA-FLS, TNF- α stimulation significantly increased the cell viability ( P < 0.05), upregulated the expressions of IL-1β, IL-6, and TNF- α , and lowered the expression of IL-10 ( P < 0.05). These changes were significantly suppressed by transfection of the cells with miR-342-3p mimics ( P < 0.05) but enhanced by transfection with miR-342-3p inhibitor ( P < 0.05)., Conclusion: The expression of miR-342-3p is decreased in the PBMCs of RA patients. A lowered expression of miR-342-3p contributes to the pathogenesis of RA by promoting inflammatory responses and migration of RA-FLS.