Abstract: Objective The study found that secondary nerve injury after cerebral ischemia-reperfusion is closely related to autophagy system. The aim of the paper is to observe the effect of mild hypothermia on cognitive impairment after cerebral ischemia-reperfusion in rats by control study. Methods The left MCOR model of rats was made by using the Longa suture method on 36 male Sprague-Dawley rats. There were 16 rats in the control group and the mild hypothermia group, and the other 4 were assigned into the sham operation group. The mild hypothermia group was given hypothermia 13-14 minutes after cerebral ischemia, while the sham operation group was not treated. The behavioral test was performed. The expression levels of Beta-amyloid precursor protein lyase-1 (BACE-1) and Microtubule-associated protein-3 were tested by immunohistochemical method. The statistical analysis was carried out by SPSS 19.0 software and P<0.05 was for a significant difference. Results The results of immunohistochemistry showed that BACE-1 increased significantly at 24 h after ischemia-reperfusion, reached a peak at around 72 h (P<0.05), and then decreased. There was no significant difference in the expression of BACE-1 between the hypothermia group and the control group (P>0.05). The expression of LC-3 increased with reperfusion for 4 hours, and its expression increased gradually with the prolongation of reperfusion time (P<0.05). The expression of LC-3 in the hypothermia intervention group was significantly higher than that in the control group (P<0.05). Neurological deficit score for sham operation was 0; for the control group there was no significant difference on the reperfusion time-point 24 h and 1 w (P>0.05), and were statistically significant on the other time points (P<0.05). Y-maze results showed that there were differences between the time points in the mild hypothermia group and the sham operation group (t=6.752, P<0.05). Conclusion The mild hypothermia has a protective effect on the survival of nerve cells after cerebral ischemia, which will improve the recovery of post-cognitive impairment; this protective effect may be associated with hypothermia-promoting the expression of LC-3 and BACE-1 in the penumbra region.