Objective To investigate the effect and mechanism of quercetin on the mitochondrial of chondrosarcoma. Methods SW1353 was randomly divided into treated group, agonist group and control group after transferring of culture. Quercetin was added into treated group, and quercetin with 740Y-P was added into agonist group, however there was only SW1353 in the control group. The relevant functions of cell and mitochondrial were detected after dealing with 48 hours including cell activity by CCK 8 kit, membrane potential (ΔΨm) by JC-1 probe, and reactive oxygen species (ROS) by ROS kit. Further, the Akt and p-Akt in signaling pathway were detected by Western blot, meanwhile the Bax and Bcl-2 of apoptosis-related proteins were also detected by Western blot.Results The cell activity in treated group(0.520±0.118) was lower than that in agonist group, F=12.543, p﹤0.05. The ΔΨm of treated group(1.449±0.082) was inferior to agonist or control group, F=96.333，p﹤0.05. The level of ROS in treated group(0.635±0.065) was under agonist or control one, F=6.850, p﹤0.05. Furthermore, the expression level of p-Akt in treated group (0.565±0.040) was less than the agonist or control one, F=283.676, p﹤0.05. To the treated group, Bax (1.329±0.104) was higher than the other two，F=36.787, p﹤0.05, however the Bcl-2 (0.544±0.038) was lower than the others, F=25.775, p﹤0.05. Conclusion Qercetin could inhibit the physiological function of mitochondrial in chondrosarcoma, and initiate mitochondria-induced apoptosis through the PI3K/Akt signaling pathway, which ultimately suppresses the multiplication of chondrosarcoma cells.