Background:This study intended to compare the expression levels of tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6) genes in active rheumatoid arthritis (RA) patients who were receiving conventional synthetic disease-modifying drugs (csDMARDs) and to find the clinical and laboratory determinants affecting TNF-α and IL-6 genes expression levels among active RA patients. Method: This was a cross sectional study that included 108 active RA patients who were receiving csDMARDs. A detailed history was reviewed for all patients in addition to a complete physical examination and assessment of the 28-joint disease activity score (DAS28). Some laboratory measures were recorded as C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and serum rheumatoid factor (RF). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure expression levels of TNF- α and IL-6 genes. Results: In active RA patients, TNF-α and IL-6 genes expression levels were significantly correlated to each other (p<0.001, r=0.788). Also, both had positive correlations with the age and DAS28 among RA patients (p<0.001). IL-6 and TNF-α expression levels were significantly higher in RA patients with high DAS28 scores (p<0.001). Most RA patients (81.5%) had relatively higher IL-6 gene expression levels than TNF-α. RA patients with relatively high IL-6 expression levels were younger in age and had shorter disease duration and less DAS28 than RA patients with relatively high TNF-α gene expression levels. In addition, they had higher CRP and RF levels. Young age was detected as a significant predictor for relatively higher IL-6 gene expression levels than TNF-α. Conclusion: most active RA patients had higher IL-6 gene expression levels than TNF-α. Young age could be considered a significant predictor for relatively high IL-6 gene expression levels among active RA patients.