To explore the effects of anesthesia induction by propofol combined with esketamine during laparoscopic total hysterectomy of patients on their postoperative early cognitive function. Methods: A total of 80 patients who wanted elective laparoscopic total hysterectomy were selected and were divided into group A and group B (40 cases in each group) according to the random sequence generated by the random number table from January 2021 to June 2021. The patients in group A received anesthesia induction by propofol combined with esketamine, and the patients in group B received anesthesia induction by fentanyl combined with propofol. The changes of mean arterial pressure (MAP) and heart rate (HR) values, the operation time, the postoperative pain visual analog score (VAS), and the adverse reactions rate of the patients in the two groups were recorded. The scores of the patients before and after surgery were conducted by Minimental State Examination (MMSE), and the situation of postoperative cognitive decline (POCD) of the patients in the two groups was assessed by Z-score method. Results: The values of MAP and HR of the patients in group A had no significantly different among the different time points, but which of the patients in group B had significantly different among different time points (P＜0.05). There was no significant difference in the postoperative VAS score of the patients between the two groups (P＞0.05). The total incidence of adverse reactions (30.0%) of the patients in group B was significantly higher than that (10.0%) of the patients in group A (P＜0.05), but there was no significant difference in the incidence of POCD (2.5% vs.2.5%) of the patients between the two groups (P＞0.05). Conclusion: Esketamine combined with propofol for anesthesia induction during laparoscopic total hysterectomy of the patients can reduce the incidence of their postoperative adverse reactions, and can stabilize their intraoperative vital signs without affecting their postoperative cognitive function.