Conclusion: Taken together, circ0085539 effectively promoted progression of osteosarcoma through sponging miR-526b-5p to release PHLDA1, strongly suggesting that in vivo intervention of circ0085539–miR-526b-5p–PHLDA1 axis could function as a promising OS-targeted therapy. Here, PHLDA1 is linked to osteosarcoma.