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Objectives The aim of this study was to assess the possible relations between serum level of prohepcidin in patients with rheumatoid arthritis (RA) and their rheumatoid anemia profiles and disease activity. Patients and methods A total of 80 patients with RA (34 male and 46 female) were enrolled. Their mean age was 43.3 ± 11.5 years, and the mean duration of the disease was 7.7 ± 7.0 years. RA disease activities were measured using Disease Activity Score 28 (DAS28). Anemia profiles were measured. Serum concentration of prohepcidin, the prohormone of hepcidin, was measured using enzyme-linked immunosorbent assay. Results The patients′ mean concentration of serum prohepcidin was 211.4 ± 5.88 ng/ml, which was significantly higher than in the control group (167 ± 5.2 ng/ml). Serum level of interleukin-6 and tumor necrosis factor-α were significantly higher in RA patients than in the healthy control group (21.11 ± 5.88 vs. 3.36 ± 1.3 pg/ml and 17.8 ± 3.7 vs. 3.7 ± 1.1 pg/ml, respectively). The prohepcidin concentration was correlated with rheumatoid factor, C-reactive protein, erythrocyte sedimentation rate, and DAS28. There was a significant correlation between prohepcidin with tumor necrosis factor-α and interleukin-6. The prohepcidin concentration was significantly higher in the patients with active RA (DAS28 > 5.1) than those with inactive-to-moderate RA (DAS28≤5.1). Serum prohepcidin concentration in patients negatively correlated with serum iron (r = −0.23, P = 0.04). However, the prohepcidin concentration did not correlate with other anemia profiles. There was no difference of prohepcidin concentration between the patients with anemia of chronic disease and those without. Conclusion Serum concentration of prohepcidin reflects the disease activity, regardless of the anemia states in RA patients, and thus prohepcidin could be used as another useful marker for RA disease activity.