Matrix metalloproteinase-1 (MMP-1) is known to be involved in the pathogenesis of glioma. It damages the extra-cellular matrix to produce invasiveness in cancer tissue, and hence has a direct effect in cancer invasion. The study aims to explore the association of single nucleotide polymorphism of -1607 MMP-1 gene with susceptibility to glioblastoma multiforme (GBM) in northern Indian subjects. One hundred and ten GBM patients and 150 healthy controls were included in this study. 1607 MMP-1 gene was studied by PCR-RFLP; different genotypes being combinations of 1G and 2G allele (1G/1G, 1G/2G and 2G/2G). 2G/2G genotype was significantly associated with GBM patients (OR, 2.24; P = 0.016; 95% CI, 1.16-4.30) as compared to controls. Prevalence of the 2G allele of -1607 MMP-1 polymorphism was significantly greater in GBM patients as compared to controls (62.3 vs 48.3%, OR, 1.76; P = 0.002; 95% CI, 1.23-2.52). This study suggests that the 2G/2G genotype and 2G allele of -1607 MMP-1 polymorphism are associated with an increased susceptibility for developing GBM.