Background: Rheumatoid arthritis (RA) is a chronic autoimmune disorder. Autophagy, a regulator of cell homeostasis, can impact innate and adaptive immune cells activation and contribute to the pathogenesis of RA. The purpose of this study was to assess the significance of autophagy in RA, by investigating the autophagy signaling Beclin-1 in RA patients. Results: In RA patients, the Beclin-1 gene expression level was higher than the healthy controls with a statistically highly significant difference (P < 0. 001) where the gene expression mean was 3.33 ± 0.45 in patients and 0.98 ± 0.070 in controls. There was a significant positive correlation between Beclin-1 gene expression and disease duration (p = 0.013*), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and rheumatoid factor (RF) titer (P = 0.018*, 0.027*, and 0.023* respectively). Beclin-1 gene overexpression is significantly correlated with disease activity parameters (DAS 28, patient and physician global health assessment). Furthermore, the Beclin-1 gene overexpression is highly correlated with the disability index, Modified Health Assessment Questionnaire (MHAQ) (P < 0.001). Conclusion The elevated autophagy-related gene Beclin-1 expression in RA patients can contribute to RA probability, high disease activity, and severity. Therefore, suppressing autophagy may be a therapeutic target for RA. Keywords Rheumatoid arthritis, Autophagy, Beclin-1, Autophagy related genes.