Abstract: objective: To investigate the effects of lidocaine on malignant proliferation, invasion and mitochondrial respiration of osteosarcoma MG-63 cells. Methods: MG-63 cells were treated with 25, 50 and 100 microns of Lidocaine and randomly divided into four groups: Lidocaine 0 microns, Lidocaine 25 microns, Lidocaine50 microns and Lidocaine 100 microns for subsequent experiments. BrdU staining was used to detect cell proliferation. Transwell detected cell invasion. Protein expression levels of Ki67, Survivin, VEGF and Vimentin were detected by western blotting. Mitochondrial membrane potential was detected by flow separator. Activity of mitochondrial respiratory complex was detected by Clark oxygen electrode method. The kit detected the content of ATP, SOD and MDA. Results: Results show that compared with Lidocaine 0 mu M group, Lidocaine50, 100 mu M group BrdU positive cells was significantly reduced（P＜0.05）, invasive cells was significantly reduced（P＜0.05）, Ki67, Survivin, VEGF, Vimentin protein levels decreased significantly（P＜0.05）, mitochondrial membrane potential decreased obviously, compound I, II, IV activity decreased significantly（P＜0.05）, ATP, SOD content decreased significantly（P＜0.05）, MDA content was significantly increased（P＜0.05）. Conclusion: lidocaine can inhibit the malignant proliferation, invasion and improve the mitochondrial function of osteosarcoma MG-63 cells.