Objective：This study aimed at the effect of tumor necrosis factor receptor-associated factor 6（TRAF6）knockdown on interleukin-17（IL-17）modulating the expression of osteoprotegerin（OPG）and receptor activator for nuclear factor-κB ligand（RANKL）in human periodontal ligament cells（hPDLCs）under hypoxia. Methods：The experiment was set as the normoxia plus IL-17 group，the hypoxia plus IL-17 group and the hypoxia group. Each group was divided into the negative control group（the TRAF6-NC group）and the disturbance group（the TRAF6-shRNA group）. The shRNA lentiviral vector was used to infect hPDLCs. The efficiency of infection was observed by inverted microscope and verified by RT-PCR. The expression of HIF-1α，RANKL and OPG in human periodontal ligament cells were detected by Western blot and RT-PCR. Results：The ratio of RANKL/OPG relative expression of RANKL and OPG protein in the hypoxia plus IL-17 group was higher than that in the hypoxia group. Under hypoxia plus IL-17 conditions，the expression of RANKL was decreased in the TRAF6-shRNA group compared with the TRAF6-NC group，and the ratio of RANKL/OPG relative expression of RANKL and OPG was decreased. Conclusion：TRAF6 is involved in the regulation of IL-17-stimulated expression of bone resorption molecules in human periodontal ligament cells in hypoxic conditions. Knocking down TRAF6 can reduce IL-17-induced expression of bone resorption molecules in human periodontal ligament cells.