Objective To observe and explore the application effect of Dexmedetomidine combined with Sufentanil in painless intestinal endoscopic submucosal dissection(ESD).Methods A total of 60 patients who underwent selective ESD in Pingxiang People′s Hospital from January 2019 to December 2020 were selected as the research subjects.According to the random number table method,they were divided into a control group and an observation group,with 30 cases in each group.Patients in the control group were given traditional intravenous anesthesia of Propofol combined with Sufentanil;while in the observation group,intravenous anesthesia of Dexmedetomidine combined with Sufentanil was used.The respiration(RR),heart rate(HR),mean arterial pressure(MAP),and pulse blood oxygen saturation(SpO2)of the two groups before induction of anesthesia(T0),2 min after administration(T1),5 min after administration(T2),10 min after administration(T3),30 min after administration(T4),and at the end of surgery(T5)were monitored.The operation time,anesthesia induction time and postoperative recovery time were recorded.The occurrence of adverse reactions during the operation and the analgesic effect of patients were observed.Results The RR,HR,and MAP of the two groups at T1-T5 were lower than those of this group at T0,and the differences were statistically significant(P＜0.05).There were no significant differences in SpO2 between T1-T5 and T0 between the two groups(P＞0.05).The MAP levels of the observation group at T1-T4 were higher than those of the control group,and the differences were statistically significant(P＜0.05).There was no statistically significant difference in MAP between the two groups at T5(P＞0.05).There were no statistically significant differences in RR,HR and SpO2 between the two groups at T1-T5(P＞0.05).There was no statistically significant difference in the operation time between the two groups(P＞0.05).The observation group had longer anesthesia induction time than the control group,while the recovery time of the observation group was shorter than that of the control group,and the analgesic effect of patients was also better than that of the control group,with statistical significance difference(P＜0.05).The incidence of hypotension,respiratory depression and body movement reactions and total incidence of averse reactions in the observation group were lower than those in the control group,and the differences were statistically significant(P＜0.05).Conclusion In painless intestinal ESD surgery,application of Dexmedetomidine combined with Sufentanil has great analgesic effect,little impact on hemodynamics,quick wake up,and few adverse reactions with a favorable application effect.