TNF–α influences lymphomagenesis by upregulating proinflammatory and antiapoptotic pathways. In this study, we evaluated the frequency of TNF–α rs1800629 (–308 G>A) polymorphism in newly diagnosed adult patients with acute lymphoblastic leukemia (ALL) and its correlation with age at diagnosis, gender and subtype of ALL. In this case control study, a total of 330 individuals were recruited, including 165 newly diagnosed adult patients with ALL, from the Radiation and Isotope Center in Khartoum (RICK) and 165 healthy normal controls. TNF–α rs1800629 polymorphism was tested through allele-specific polymerase chain reaction (PCR) assay. The frequency of the rs1800629 GA genotype was high (70.9% vs. 60%, OR = 1.84) in the patient group as compared to healthy controls, whereas GG and AA genotypes did not exhibit any statistically significant difference between controls and patients. Based on subtype, GG and GA rs1800629 genotypes showed increased risk of B-ALL (OR 0.46 and 2.12, respectively), whereas rs1800629 GG, GA and AA genotypes did not show any disease association with T-ALL (p > 0.05). Age at diagnosis and gender did not exhibit any association of rs1800629 with ALL in the patient group. In conclusion, rs1800629 is associated with high risk of adult B-ALL, with an insignificant effect of age at diagnosis and gender.