Objective:To evaluate the relationship between the mechanism of curcumin attenuating lidocaine-induced neurotoxicity and autophagy.Methods:In vitro human neuroblastoma SH-SY5Y cells at the logarithmic phase were divided into 3 groups ( n=12 each) using the random number table method: blank control group (C group), lidocaine group (Lid group), and curcumin + lidocaine group (Cur + Lid group). The cells were incubated with complete medium containing 1.0 μmol/L curcumin for 24 h, and the other groups were incubated with fresh medium for 24 h under the same conditions in Cur+ Lid group. Then the medium was incubated with the complete medium containing 4.0 mmol/L lidocaine for 24 h in Lid and Cur+ Lid groups, and the medium was replaced with the fresh medium and the cells were incubated for 24 h under the same conditions in group C. At the end of incubation or culture, the cell viability was detected by CCK-8 method, the level of autophagosomes was detected by the MDC method, and the expression of P62, microtubule-associated protein light chain 3-Ⅱ (LC3-Ⅱ) and LC3-Ⅰ was detected by Western blot, and the LC3-Ⅱ/LC3-Ⅰ ratio was calculated. Results:Compared with group C, the cell viability was significantly decreased, the level of autophagosomes was increased, the expression of LC3-Ⅱ was up-regulated, the expression of LC3-Ⅰ was down-regulated, the LC3-Ⅱ/LC3-Ⅰ ratio was increased, and the expression of P62 was down-regulated in Lid and Cur+ Lid groups ( P<0.05). Compared with Lid group, the cell viability and level of autophagosome were significantly increased, the expression of LC3-Ⅱ was up-regulated, the expression of LC3-Ⅰ was down-regulated, the LC3-Ⅱ/LC3-Ⅰ ratio was increased, and the expression of P62 was down-regulated in Cur+ Lid group ( P<0.05). Conclusions:The mechanism by which curcumin reduces the neurotoxicity induced by lidocaine may be related to the activation of autophagy.