Systemic lupus erythematosus (SLE) is a chronic complex autoimmune disease. It results from interaction of genetic, environmental and hormonal factors. Genome Wide Association (GWA) studies have proved the association of multiple STAT4 gene polymorphisms with SLE in different populations. Subjects & methods: The study enrolled 50 Egyptian females, classified into 2 groups: 30 SLE patients and 20 apparently healthy individuals. STAT4 gene C>G (rs7582694) polymorphism was analyzed by PCR-RFLP (Polymerase chain reaction - Restriction fragment length polymorphism) technique. Results: The frequency of minor allele C of the STAT4 (rs7582694) polymorphism was higher in SLE patients than control group but with no statistically significant difference between the two studied groups (P=0.518). There was neither association between genotypes and SLE nor SLEDAI activity grades. Conclusion:STAT4 gene C>G (rs7582694) polymorphism is not associated with the predisposition to SLE or disease activity in the studied group of Egyptian SLE patients.