Non-Hodgkin lymphoma includes several lymphoproliferative malignant diseases with different clinical and histological appearances. The origin of the lymphoma cells in NHL is most commonly B-cells and less frequently from T cells.Matrix metalloproteinases (MMPs, matrixins) are family of secreted and membrane-bound zinc-dependent endopeptidases that have the combined capacity to degrade all the components of the extracellular matrix.MMP enzymes are strongly involved in a kaleidoscope of normal, pathological, physiological processes such as embryogenesis, normal tissue remodeling, wound healing, and angiogenesis, they play also a vital role in diseases such as atheroma, arthritis, cancer, and tissue ulceration. On the basis of substrate specificity and homology, MMPs can be divided into 6 groups: collagenases, gelatinases, stromelysins, matrilysins, membrane-type MMPs (MT-MMPs), and other MMPs.Abnormal activity of MMPs has been implicated in many disease processes. MMPs are considered key players in the regulation of both cell–cell and cell–ECM interactions, and the elucidation of their potential as drug targets in disease or as important features of the repair process will be dependent upon careful analysis of their role in different cellular locations and at different disease stages.Genetic polymorphisms within these proteins can alter their expression level or interaction with other essential proteins or receptors, and may be involved in the development of lymphoid malignancies.The aim of the current study was to investigate the effect of an inherited genetic polymorphism at MMP2- 1306C/T and MMP2 -735C/T on the predisposition to NHL in Egyptian patients.To achieve this aim, genotyping for these genes was performed by restriction fragment length polymorphism- polymerase chain reaction (PCR-RFLP (technique in 100 Egyptian NHL patients. One hundred age and gender matched healthy volunteers were subjected to the same analysis as a control group.MMP2 -735C/T genotyping revealed that MMP2 -735C/T CC, CT, TT genotypes were detected in 85%, 15%, and 0% of the controls respectively, while it was detected in 70%, 23% and 7% of NHL patients.MMP2 -1306C/T genotyping revealed that MMP2 -1306C/T CC, CT, TT genotypes were detected in 98%, 1%, and 1% of the controls respectively, while it was detected in 92%, 5% and 3%of NHL patients.MMP2- 735 C/T mutant was significantly higher in NHL subjects when compared to controls, and was associated with increased risk of NHL about two and half folds increase (p value<0.001). No statistically significant difference was noticed between NHL patients having the normal and mutant genotypes as regards their age, sex, clinical or laboratory data.Combined genotype analysis revealed that co-inheritance of MMP2 735C/T and MMP2 1306C/T polymorphisms was associated with near three folds increase in NHL risk (OR= 2.867, 95% CI= 1.480-5.554).In conclusion, the results obtained by the current study together with the previous researches concerning MMP-2 (735 C/T) and MMP-2(1306 C/T) genetic polymorphisms in NHL provide additional evidence of the role played by these genes in the susceptibility to NHL.