Objective: To observe the anesthetic effect of dexmedetomidine combined with the mixture of propofol and etomidate on painless gastroscopy in children. Methods: A total of 80 pediatric patients who underwent painless gastroscopy in the Guangxi Minzu Hospital from January 2019 to September 2020 were randomly divided into two groups, A and B, with 40 patients in each group. Group A was given A mixture of etomidate 20 mg and propofol 0.2g, Dexmedetomidine was pumped into group B 10min before surgery, 0.4 g/kg. HR, SBP, DBP, SpO2 and BIS were continuously monitored after entering the room. The doses of propofol and etomidate were recorded, as well as the time of waking and leaving the hospital. Adverse reactions such as hypotension, hypoxemia, nausea, vomiting and dizziness were recorded too. Results: Compared with group A, the dosage of propofol and etomidate in group B was significantly reduced (P < 0.001), the time of waking and out of the chamber were significantly shortened (P < 0.001), the body movement in the incidence of intraoperative was significantly reduced (P < 0.001), and the nausea, vomiting and dizziness in the incidence of postoperative were significantly reduced (P < 0.05). Conclusion: Dexmedetomidine combined with propofol and etomidate mixture can be safely used in painless gastroscopy in children, which can significantly reduce the dosage of propofol and etomidate, reduce the occurrence of adverse reactions, and shorten the time of resuscitation and discharge.