Systemic lupus erythematosus (SLE) is a systemic autoimmune illness caused by the collapse of immunological tolerance systems. It is a multisystemic autoimmune disease. Complex dysfunction in the innate and adaptive immune systems is a feature of SLE. The Toll-like receptor 9 gene single nucleotide polymorphisms have been linked to systemic lupus erythematosus (SLE) in many studies. Our study aimed to identify and compare single nucleotide polymorphisms (SNP) in theTLR9 (rs187084) genes among Egyptian SLE patients and healthy controls. Blood samples from 100 SLE subjects and 100 controls were obtained for our case-control study. After DNA extraction, we performed purification test. the extracted samples were processed for the examination of single nucleotides gene polymorphism of TLR9 (rs187084) by restriction fragment length polymorphism (RFLP) reaction. Our results showed that no association were detected between TLR9 rs187084 and SLE development. Only one significant association were found between TLR9 rs187084 TC genotype and malar rash.