Single nucleotide polymorphisms in the promoter regions of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinase (TIMP) genes are associated with an adverse outcome in some cancers. We examined three polymorphisms: −1306C/T and −735C/T in MMP-2 and −418G/C in the TIMP-2 gene, using chain reaction restriction fragment length polymorphism typing analysis in 575 patients with non-Hodgkin's lymphoma (NHL). We examined the possible correlations between the three polymorphisms (MMP-2 (−1306C/T and −735C/T) and TIMP-2 gene (−418G/C)) and the clinical significance and survival rate in patients with NHL. The incidence of the CT, TT+CT genotypes and T allele of −735C/T was significantly higher in stage III and IV patients compared to stage I and II patients. In cases with bone marrow infiltration, the TT genotypes of the −1306C/T gene were significantly less frequent compared to CC genotypes. The CT, TT and CT+TT genotypes and T allele in patients exhibiting the −1306C/T polymorphism were significantly less frequent in patients with a large tumor size compared to a smaller tumor. The TT genotypes of the −735C/T polymorphism were more common in patients with a large tumor compared to those with a smaller tumor. The frequency of the −1306C/−735T haplotype in patients with a smaller tumor size was significantly higher compared to patients with a large tumor. The −1306T/−735C and −1306C/−735C haplotypes were significantly less frequent in patients with B-symptoms compared to those without. Interestingly, patients with the −735CT genotype exhibited a lower rate of survival. Our results demonstrate that certain MMP-2 and TIMP-2 gene polymorphisms potentially effect the progression or assessment of prognosis for NHL. This research warrants further, larger scale studies.