【Abstract】Objective To explore the mechanism of bupivacainemediated PI3K/AKT/mTOR pathway in the induction of autophagy and apoptosis of colon cancer SW480 cells and its inhibitory effects on formation of xenografts in nude mice. Methods Colon cancer SW480 cells were divided into Control group and Bupivacaine groups (025, 05, 1 mM). After 24 h of cell treatment, cell proliferation was detected by Edu staining. Apoptosis was detected by flow cytometry. Western blot was used to detect the related proteins expressions of proliferation, apoptosis, autophagy and signaling pathway. Nude mice models of colon cancer were established and randomly divided into Bupivacaine groups (5, 10, 20 mg) and Control group, and they were intraperitoneally injected with 5, 10 and 20 mg/kg of Bupivacaine and an equal volume of normal saline once daily. After 30 d of continuous treatment, the mice were sacrificed, tumors were gotten to weigh. The positive expression level of Ki67 protein in tumor tissues was detected by immunohistochemistry. The survival curves of nude mice in each group were drawn. Results With the increase of Bupivacaine concentration, the proliferation quantity of SW480 cells and expression levels of proliferationrelated proteins Ki67 and PCNA were decreased gradually（F=94068, 160905, 49255，P＜005）, and were lower than those in Control group (P＜005). The apoptosis quantity of SW480 cells and expression levels of apoptosisrelated proteins Caspase3 and Caspase9 were increased gradually（F=30948, 110730, 233550，P＜005）, and were higher than those in Control group (P＜005). With the increase of Bupivacaine concentration, the relative protein expression levels of Beclin1 and ATG8 in SW480 cells, LC3II/LC3I ratio and positive number of LC3 were increased gradually（F=65287, 112337, 50602 and 26690，P＜005）, and were higher than those in Control group (P＜005). The relative protein expression level of p62 and ratios of pPI3K/PI3K, pAKT/AKT and pmTOR/mTOR were gradually decreased（F=33276, 98246, 102488 and 58051，P＜005）, and were lower than those in Control group (P＜005). After 30 days of administration, The tumor mass, Ki67 positive cell ratio and 30d survival rate in Bupivacaine administration groups were lower than those in Control group (P＜005). Conclusion Bupivacaine can inhibit the proliferation of colon cancer SW480 cells, induce the occurrence of autophagy and apoptosis, and inhibit the formation of xenografts in nude mice. Its role mechanism may be related to the inhibition of PI3K/AKT/mTOR pathway.