Non-Hodgkin lymphoma comprises a group of closely related yet heterogeneous diseases. There is evidence that genetic susceptibility plays a role in lymphomagenesis. The aim of the current study was to investigate the possible association between IL-2-330T/G and IL-10-1082A/G genetic polymorphisms and the susceptibility to B-cell Non-Hodgkin Lymphoma in a group of Egyptian patients. To achieve our aim, genotyping of the two genes was performed by PCR technique for 100 adult B-NHL patients and 100 age and gender matched healthy controls. The study revealed that the frequency of IL-2-330T/G polymorphic genotypes (TG & GG) was higher in B-NHL patients than controls (80% vs 58%) and conferred almost threefold increased risk of B-NHL in Egyptians (OR=2.90, 95%CI=1.54-5.44, p=0.001). As regards the frequency of IL-10-1082A/G polymorphic genotypes (AG&GG), statistical analysis revealed that there was no statistically significant difference in the distribution of the polymorphic genotypes between B-NHL patients and the control group. Co-inheritance of the polymorphic variants of IL-2 and the wild genotype of IL-10 conferred almost sixfold increased risk of B-NHL (OR= 5.75, 95%CI= 1.39 – 23.72, p=˂0.016) and co-inheritance of the polymorphic variants of both genes conferred fivefold increased risk of B-NHL (OR= 5.43, 95%CI= 1.44 – 20.45, p=0.012). IL-2 polymorphic genotypes were higher in patients with aggressive B-NHL than controls (78.5% vs 58%) and conferred almost threefold increased risk of aggressive B-NHL (OR= 2.64, 95%CI= 1.35 –5.15, p=0.004). However, IL-10-1082 polymorphic genotypes showed no statistically significant difference between the two groups. The frequency of IL-2 variant genotypes was higher in patients with indolent B-NHL subtypes than controls (85.7% vs 58%) and conferred fourfold increased risk of indolent B-NHL (OR= 4.34, 95%CI= 1.20 –15.71, p=0.017). However, IL-10 polymorphic genotypes did not show any statistically significant difference between the two groups. Regarding DFS, all potentially known prognostic factors did not affect the disease free survival of B-NHL patients. Also, the polymorphic genotypes of either IL-2-330T/G or IL-10-1082A/G had no effect on DFS of those patients. In conclusion, IL-2-330T/G genetic polymorphism might be considered as a genetic susceptibility factor for B-NHL in Egyptians, while IL-10-1082A/G polymorphism was not associated with increased risk of B-NHL.