Toll-like receptors are a family of pattern recognition receptors which have an important role in activation of innate and acquired immune responses. NHL has been associated with immunological defects. The link between the immune-dysregulation and NHL suggests that genetic polymorphisms in TLRs genes could be considered as risk factor for NHL. The purpose of the current study was to investigate the association between genetic variation in the Toll Like receptors 2 and 9 genes and the susceptibility to B-cell NHL in Egypt. The present study included 100 B-NHL patients and 100 healthy controls. Genotyping of TLR2-1350 T/C and TLR9-1237 T/C were done by PCR-RFLP technique. The frequency of TLR2- 1350T/C polymorphic genotypes in B-NHL patients was 18% for the heteromutant genotype (TC) and 1% for the homomutant genotype (CC). There was no statistical difference in the distribution of the different genotypes of TLR2 between B-NHL patients and controls. As for TLR9, the frequency of the heteromutant genotype (TC) was 58% and the homomutant genotype (CC) was 1% in B-NHL patients. The frequency of TLR9-1237 T/C polymorphic variants was significantly higher in B-NHL patients compared to the controls. Calculated risk estimation revealed that TLR9-1237 TT heterotype conferred almost 4 folds increased risk of B-NHL (OR=4.09, 95% CI=2.25-7.45). This study revealed that TLR 9 heteromutant genotype (TC) can be considered as a molecular risk factor for B-NHL; however, TLR 2 gene polymorphism did not confer increased risk of B-NHL among Egyptians.