Systemic lupus erythematosus (SLE) is a complicated autoimmune illness that affects several systems. It is multifaceted, encompassing epigenetic, genetic, ecological, and environmental components. Primarily, it activates both innate and adaptive immunity. This study examined the relationship of TNF-α-308 G/A (rs1800629) polymorphisms in SLE patients. The study involves 100 participants, grouped into two primary groups: 50 RA sufferers and 50 healthy controls. All subjects were genotyped for TNF–α rs1800629 (G/A) using allele-specific PCR(ASP). Genotype and allele frequency results of TNF-α -308 G/A (rs1800629) gene polymorphisms were examined under codominant, dominant, and recessive models. The SLE patients with heterozygous genotype (G/A) those of the (GA + AA) genotypes and under dominant pattern, SLE patients had substantially greater odds than those in the control group (OR: 2.49, CI 95%: (1.01-6.12), P<0.037) and (OR: 2.79, CI 95%: (1.22-6.39), P<0.012), respectively. The recessive model was found to exhibit no significant variation (OR: 2.55, CI 95%: (0.62-10.49), P< 0.69). The allele (A) frequency was observed to be significantly (OR: 2.41, CI 95%: (1.24-4.69) P< 0.0072) higher in SLE patients (33%) in comparison with the control group (17%). The results of this study suggest that the 'A' allele of the TNF-α (rs1800629) G/A polymorphism is significantly associated with an increased risk of SLE in the studied population.