Consistent with the above findings, we found that miR-381-3p enhanced DXR sensitivity of osteosarcoma cells, and SNHG15 accumulation reversed the inhibitory effects of miR-381-3p overexpression on the proliferation, DXR resistance, and autophagy of osteosarcoma cells, demonstrating that SNHG15 contributed to the DXR resistance of osteosarcoma cells through sponging miR-381-3p. The gene discussed is SNHG15; the disease is osteosarcoma.