In this study, we aimed to determine whether TLR-9 T-1486C SNP was associated with susceptibility to OA in the Turkish population. The study group comprised 272 patients with Grade 2-3-4 knee OA according to the Kellgren-Lawrence scoring system and the control group was formed of 296 individuals with Grade 0-1. The TLR-9 genotype were assessed by real-time polymerase chain reaction. An analysis of TLR-9 promoter -1486T/C polymorphism revealed that the -1486CC genotype appeared to have a higher risk for OA and -1486TT and -1486CT genotypes have a protective effect against the development of OA (crude OR=0.473, 95% CI=0.297-0.754, p=0.002, adjusted OR=0.531, 95% CI=0.326-0.864, p=0.011). This study indicate that there is a correlation of TLR-9 T-1486C gene polymorphism with advanced knee OA in a Turkish population. Changed in TLR expression due to different allelles may cause osteoarthrith development outcome cartilage degeneration. (c) 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2484-2489, 2017.