Asthma is a chronic respiratory disease leading to morbidity and impaired quality of life worldwide. TNF-α cytokine responsible for the smooth muscle activation and late-phase airway hyper responsiveness. So this study aimed to investigate TNF-α polymorphisms situated at positions –308 G/A with their serum level and asthma severity. A case–control study included 40 asthmatic patients 16 females and 24 males and matched with age and gender 40 healthy subjects as a control group. Blood samples were collected from both groups, genomic DNA was extracted from peripheral blood for further molecular study. The study appeared that TNF-α-308 G/A significantly (P<0.05) high frequencies of homozygous AA, and A allele carrier in asthmatic patients, in contrast homozygous GG genotype and G allele appear at low frequency with patients. The data showed that genetic variants of the TNF-α affect the TNF-α production and associated with the severity of asthma, AA and AG genotype associated with high serum level (58.2 pg/ml and 49.5 pg/ml) respectively and GG genotype associated with low serum level (24.06pg/ml).The study confirmed the distinct role of TNF-α in cases of asthma compared to healthy controls with significantly higher level among patients, mean serum level for patients and control were (50.3 and 5.88 ) pg/ml respectively. Also, mean serum levels of TNF-α were significantly higher in asthmatic patients that suffering from allergic rhinitis(65.39 pg/ml) compared to non-rhinitis patients (34.97pg/ml). In conclusion, TNF-α-308 GG, genotype contribute to the predisposition of asthma and there was significant association among genotype of this gene and level of cytokine as well as development of the disease. Also observed an association between this gene and serum level of cytokine. AA, AG genotype and allergic rhinitis consider a risk factor of asthma and progress the disease.