〔Abstract〕 Objective This work mainly studied the effects of acute sleep deprivation(SD) on anxiety and depression behavior in mice, and explored possible molecular mechanisms. Methods 33 male 8-week-old C57BL/6 mice were randomly divided into environment control(EC) group and a SD group.The open field test and elevated plus maze test were used to evaluate their spontaneous and anxiety behavior, while the forced swimming test and tail suspension test were used to detect depression behavior in mice.The expression of neuroinflammatory proteins and the levels of autophagy-related proteins were detected by Western blot method. Results Behavioral results showed that comparing to the EC group, the total distance traveled by mice in the SD group significantly increased in the open field test(P<0.01),while the number of crossings and time spent in the central area did not show significant differences.Results from the forced swimming test showed that immobility time significantly increased in the SD group mice(P<0.01),but there were no significant differences in tail suspension and elevated plus maze test.Western blot results showed that comparing to the EC group, the levels of NLRP1,TNF-α,IL-1β,IL-18,and autophagy protein p62 in the hippocampus of the SD group mice significantly increased, while the levels of Atg5,Atg7 decreased significantly, and the phosphorylation level of AMPK also decreased significantly. Conclusion SD may induce depression-like behavior in mice by inhibiting the AMPK-autophagy signaling pathway in the hippocampus and upregulating neuroinflammatory levels.