Objective: Interferon (IFN) signaling, and excessive apoptosis have a well-established role in systemic lupus erythematosus (SLE) pathogenesis. Long non-coding RNA (lncRNA) growth arrest-specific transcript 5 (GAS5) has been linked to excessive apoptosis and upregulation of IFN genes. We aimed to investigate the expression of IFN-stimulated genes in SLE patients compared to healthy controls, and to assess their association with lncRNA GAS5 and clinical characteristics of SLE. Methods: The study included 30 SLE patients and 20 controls. IFN-stimulatory genes (interferon-induced protein 44-like [IFI44L] gene, MX dynamin like GTPase 1 [MX1], IFN-induced protein with tetratricopeptide repeats 1 [IFIT1]) and GAS5 expression levels in plasma were estimated by quantitative real-time polymerase chain reaction. IFN signature score was calculated. Results: IFIT1 gene expression and IFN signature score were significantly higher in SLE patients compared to controls (p<0.001, p<0.001, respectively). LncRNA GAS5 positively correlated with IFIT1 expression (p<0.001) and IFN signature score (p=0.005).No significant associations were found between IFN gene expression or IFN signature score and disease activity (Systemic Lupus Erythematosus Disease Activity Index 2000, SLEDAI-2K) or organ damage (Systemic Lupus International Collaborating Clinics/ American College of Rheumatology Damage Index, SDI). IFI44L expression was significantly higher in SLE patients with secondary antiphospholipid syndrome (p=0.040). Conclusion IFN signature is a potential biomarker for SLE diagnosis, but it can’t be relied on for the assessment of activity or damage. The correlation between lncRNA GAS5 and IFN-related gene expression suggests a possible role for GAS5 in the IFN pathway in SLE.