Objective:This study aims to investigate the molecular mechanism of osteosarcoma chemotherapy sensitivity regulation of circ_0001246 via targeting miRNA30a. Methods:The MG63 and U2OS cells were randomly allocated into three groups in 6-well plates respectively,including non-transfection group(blank group), siRNA negative control transfection group(NC group),and siRNA transfection group(circ_0001246 siRNA). The transfection efficiencies were evaluated by fluorescence inverted microscope. Expression Level of circ_0001246 and miRNA30a were detected. Osteosarcoma chemotherapy sensitivity were detected by annexin V-FITC/7AAD apoptosis double staining. Function of circ_0001246 to adsorb miRNA30a were verified by luciferase reporter gene assay. Results: MiRNA30a expression in the circ_0001246 siRNA transfection group were significantly up-regulated compared to the NC group and blank group(P < 0.05). We found circ_0001246 and miRNA30a were inversely expressed. Osteosarcoma chemotherapy sensitivity in the circ_0001246 siRNA transfection group were significantly up-regulated compared to the NC group and blank group(P < 0.05). circ_0001246 could adsorb miRNA30a by direct base pairs. Conclusion: Circ_0001246 is an osteosarcoma related oncogene. Targeted inhibition of circ_0001246 expression in osteosarcoma can enhance the chemotherapy sensitivity of tumor cells to etoposide-VP16. One of the mechanisms is the negative regulation of the miRNA30a expression by the adsorption function of circ_0001246.