Propofol anesthesia contributes to the postoperative cognitive dysfunction which affects around 20% of surgical patients. The underlying molecular mechanism for propofol anesthesia induced cognitive dysfunction is not clearly elucidated. In this study, cognitive function of adult mice which were repeatedly injected with propofol was assessed using water maze test. We found that 25 mg/kg and 50 mg/kg propofol significantly reduced the percentage of swimming time in target quadrant and number of platform crossings, and increased the distance of swimming path and escape latency. Previous studies reported that repeated propofol treatment inhibited the expression of phosphor-Erk in neonatal rats. To explore the influence of propofol on phosphor-Erk expression in prefrontal cortex of adult mice, Western blot was used in this study. The results indicated that expression of phosphor-Erk was decreased by injections of propofol (25 and 50 mg/kg). In addition, the expression of miR-34a, which could be regulated by phosphor-Erk, was upregulated by propofol. Finally, mice were simultaneously with propofol (25 mg/kg) and curcumin (20 mg/kg), a phosphor-Erk agonist. And we revealed that curcumin administration could attenuate cognitive dysfunction caused by propofol.