Objective To explore the mechanism of autophagy in sevoflurane‑induced neuronal apoptosis in the hippocampus of aged mice. Methods According to the random number table method, sixteen 18‑month‑old BL/C57 mice were divided into two groups (n=8): a sevoflurane group and a control group. The sevoflurane group inhaled 47.5% air+2.5% sevoflurane+50% oxygen for 3 h, while the control group inhaled 50% air+50% oxygen for 3 h. Then, 24 h after modeling, the novel object recognition experiment was performed, and the brains were removed to collect the hippocampus. Nissl staining was performed to detect the apoptosis of neurons in the hippocampus, and Western blot was used to detect the levels of autophagy‑related proteins in neurons [microtubule‑associated protein (LC3)Ⅱ/LC3Ⅰ, Becline‑1, and p62]. Furthermore, according to the random number table method, eighteen 18‑month‑old BL/C57 mice were divided into three groups (n=6): a sevoflurane+3‑methyladenie group (group M, intraperitoneal injection of 3‑methyladenine 2 h before inhaling anesthesia), a sevoflurane+rapamycin group (group R, intraperitoneal injection of rapamycin 24 h and 2 h before inhaling anesthesia), and a sevoflurane+normal saline group (group N, intraperitoneal injection of 100 μl normal saline 2 h before inhaling anesthesia). After intraperitoneal injection and sevoflurane treatment, Nissl staining was used to detect the apoptosis of hippocampal neurons, and Western blot was used to detect the level of autophagy related proteins (LC3Ⅱ/LC3Ⅰ, Becline‑1, p62) in hippocampal neurons. Results Compared with the control group, the sevoflurane group showed significant decreases in the recognition rate and resolution coefficient of novel objects (P<0.05), increases in hippocampal neuronal apoptosis (P<0.05), increases in the levels of LC3Ⅱ/LC3Ⅰ and Becline‑1 (P<0.05), and decreases in the amounts of p62 protein (P<0.05). Compared with group N, group M presented decreases in the levels of LC3Ⅱ/LC3Ⅰ and Becline‑1 (P<0.05), increases in the amounts of p62 (P<0.05), and increases in neuronal apoptosis in the hippocampus (P<0.05); group R presented increases in the levels of LC3Ⅱ/LC3Ⅰ and Becline‑1 (P<0.05), decreases in the amounts of p62 (P<0.05), and decreases in neuronal apoptosis in the hippocampus (P<0.05). Conclusions After sevoflurane inhalation, aged mice show decreases in the recognition rate and resolution coefficient of new objects, and increases in neuronal apoptosis in the hippocampus, with activation of autophagy at the same time, which negatively inhibits neuronal apoptosis and exerts a neuroprotective effect.