Osteosarcoma is an aggressive malignant neoplasm and cancerous bone tumor. Quercetin is a well-known flavonoid abundant in vegetables, fruits, grains, leaves, and red onions. In the present study, we evaluated the effects of quercetin-induced inhibition of parathyroid hormone receptor 1 (PTHR1) on proliferation, migration, and invasion in U2OS and Saos^-2 cells. Following incubation with quercetin (20, 40, 60, 80, or 100 μM) for 48 h, the cell viability of U2OS and Saos^-2 cells were significantly reduced in a dose-dependent manner. Additionally, there were significant decreases in cell adhesion, invasion, and migration as well as reduced cell viability at higher concentrations of quercetin. Furthermore, the mRNA expression levels of matrix metalloproteinases (MMP)-2 and -9 were attenuated, whereas the mRNA expression levels of tissue inhibitors of metalloproteinases (TIMP)-1 and -2 were elevated. Quercetin treatment also significantly reduced the mRNA expression levels of PTHR1 by 0.27-, and 0.55-fold at 80, and 100 μM, respectively, whereas 0.19 and 0.41 folds in Saos^-2 cells. PTHR1 protein expression in U2OS cells was reduced by 0.19-, and 0.43-fold at 80, and 100 μM of quercetin, respectively (P < 0.05), whereas 0.17 and 0.35 folds in Saos-2 cells. Immunofluorescence analyses revealed reduced expression of PTHR1 following treatment with quercetin. PTHR1 expression in U2OS cells was reduced by 0.18-, and 0.41-fold at 80, and 100 μM, respectively, whereas 0.15 and 0.38 folds in Saos^-2 cells. The knockdown of PTHR1enhanced quercetin-inhibited proliferation and invasion. Taken together, the present findings indicate that quercetin reduced human metastatic osteosarcoma cell invasion, adhesion, proliferation, and migration by inhibiting PTHR1.