Background: MicroRNAs play a crucial role in the regulation of immune response. We hypothesised roles for serum miR-210 and miR-155 in the diagnosis of rheumatoid arthritis (RA) and relationships with the clinical and laboratory variables including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), anti-cyclic citrullinated peptide (CCP) antibodies, tumour necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β). Methods: MiR-210 and miR-155 levels were identified by real-time polymerase chain reaction (PCR). TNF-α and IL-1β were measured by enzyme-linked immunosorbent assay and routine markers by standard techniques in 100 patients with RA and 100 individuals as healthy controls. Disease activity in the patients was assessed by DA-S28. Results: MiR-210 was lower in RA compared to controls [median/IQR 0.96 (0.8–1.24) vs. 4 (1.28– 3.93), p < 0.001]. miR-210 correlated inversely with clinical and laboratory variables including TNF-α and IL-1β (both r = −0.96, p < 0.001). MiR-155 expression was increased in RA compared to controls [median/IQR 6 (3.5–8.1) vs. 1.0 (0.95–1.6), p < 0.001] and correlated with TNF-α and IL-1β (both r = 0.94, p < 0.001). In multivariate analysis, miR-210 and miR-155 were both independent diagnostic markers for RA, and both were associated with RA disease activity. Conclusion: Serum miR-210 and miR-155 levels are independent diagnostic markers for RA, outperforming several routine indices and reflect disease activity. Thus, miR-210 and miR-155 might serve as non-invasive biomarkers for the diagnosis of RA.