Background: Rheumatoid arthritis (RA) represents a worldwide health concern as it leads to joint deformities or even permanent disability. As epigenetic directors of biological signalling mechanisms, the erratic expression of various micro-RNAs (miRNAs) is strongly associated with RA. Objectives: The purpose of the current research was to assess the significance of miRNA-146a and miRNA-155 as predictors of the development of RA. We also assessed their promising application as biomarkers for RA disease activity. Methodology: This case-control study included 62 subjects (31 RA patients and 31 healthy controls). Participants sera were used for laboratory tests [anti-cyclic citrullinated peptide (anti-CCP), rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP)] and for the measurement of miRNA-146a, and miRNA-155 gene expression. Results: In RA patients, levels of miRNA-146a and miRNA-155 were significantly higher than in controls (P<0.001). The receiver operating characteristic (ROC) curve analysis showed that miRNA-146a could predict RA with area under curve 0.857, sensitivity 77.4% and specificity 80.6% (P<0.001) at 95% confidence interval (CI) (0.765 – 0.95). MiRNA-155 could predict RA with area under curve 0.829, sensitivity 77.4% and specificity 67.7% (P<0.001) at 95% CI (0.727 – 0.932). Active RA patients expressed more miRNA-146a and miRNA-155 than the inactive group. There was a significant positive correlation (P<0.05) among miRNAs-146a and155 expression levels and DAS-28 score in RA patients. MiRNA -146a was found to increase the risk of active RA significantly independently by 2.023 folds. The ROC curve showed that miRNA -146a is useful for prediction of RA disease activity with area under curve 0.905, sensitivity 91.3% and specificity 87.5% (P<0.001) at 95% CI (0.791 – 1). Conclusion: MiRNA-146a and miRNA-155 expressions were remarkable in RA patients and could be recognized as potential biomarkers for early RA diagnosis. However, miRNA- 146a expression is an independent risk for active RA and could be a valuable biomarker to predict RA disease activity