Aim: Matrix metalloproteinase-1 (MMP-1) polymorphisms are related to elevated susceptibility of tumor development and poor prognosis of patients in several cancers. The current study aimed to determine whether MMP-1 polymorphisms were associated with the risk and prognosis of osteosarcoma patients. Methods: MMP-1-1607 1G/2G genotype variants were identified using denaturing high performance liquid chromatography (DHPLC) and DNA sequencing techniques. chi(2) test was used to evaluate the association of the polymorphisms and clinical characteristics. Results: The Kaplan-Meier and Cox regression analysis were performed to detect the prognostic values of MMP-1 polymorphisms. Our findings exhibited that 1G/2G (OR=4.219, 95% CI=2.040-8.728, P<0.05) and 2G/2G (OR=8.770, 95% CI=3.657-21.030, P<0.05) variants presented more frequently in osteosarcoma patients while 1G/1G was less common in osteosarcoma patients. Moreover, there was significant association between MMP-1-1607 1G/2G genotype and clinicopathologic characteristics including Enneking stages, distant metastasis, response to chemotherapy and recurrence while no relations were found in gender and age. Conclusions: Osteosarcoma patients with 1G/2G genotype and 2G/2G. Genotype presented a shorter survival time compared with those with 1G/1G via Kaplan-Meier analysis (P=0.000). Cox regression analysis suggested that MMP-1-1607 1G/2G (HR=3.657, 95% CI=1.020-13.109, P=0.047) and 2G/2G (HR=12.028, 95% CI=3.089-46.861, P=0.000) genotypes and recurrence (HR=2.513, 95% CI=1.253-5.040, P=0.009) might be potential prognostic markers of osteosarcoma patients. Taken together, our studies demonstrated that MMP-1 polymorphisms was related with the risk of osteosarcoma and possessed important prognostic value.