Objective To investigate the effect of hippocampal autophagy on sevoflurane-induced cognitive impairment in aged rats and its possible mechanism. Methods Seventy-two Sprague-Dawley rats were randomly divided into 6 groups: CON, RAP, CQ, SEV, SEV+RAP, and SEV+CQ. The following method were used to collect data from each group: blood gas indexes; learning and memory ability testing by Morris water maze; ultrastructural changes of hippocampal neurons under transmission electron microscopy; apoptosis of hippocampal CA1 neurons observed by terminal deoxynucleotidyl transferase dUTP nick end labeling; quantification of LC3 mRNA expression by reverse transcription- quantitative PCR; and protein expression of p62, LC3, Caspase3, Bax and Bcl-2 in the hippocampus detected by Western blot. Results There were no significant differences in arterial blood gas result in the 6 groups of rats ( P> 0. 05). Compared with the CON group, in the SEV group the escape latency was prolonged (P < 0. 01), the percentage of target quadrant time was shortened (P < 0. 05), and the number of crossing platforms was reduced ( P < 0. 01), while the expression of p62, cleaved caspase-3 and Bax protein increased in the hippocampus (P< 0. 05), Bcl-2 decreased (P< 0. 01), and the number of autophagic vesicles and the rate of apoptosis were increased in the hippocampus (P< 0. 01). Compared with the SEV group, the escape latency of the SEV+RAP group was decreased (P< 0. 01). Additionally, the expression of p62, p-mTOR, p-s6k1, cl-caspase-3 and Bax protein were all decreased in the hippocampus (P< 0. 05), while the expression of LC3 mRNA and bcl-2 protein increased (P< 0. 01), and the number of autophagic vesicles and the rate of apoptosis increased (P< 0. 01) in the hippocampus. Conclusions Cognitive dysfunction caused by sevoflurane anesthesia in elderly rats may be related to impaired autophagy in hippocampal neurons.