Abstract: Objective To explore the effect of dexmedetomidine combined with sufentanil on the pain caused by burn and the expression of P2X₇ receptor in monocyte. Methods A total of 152 patients in the Burns of Taizhou Hospital of Wenzhou Medical University between December 2015 and December 2017 were selected and divided into control group (76 cases) and observation group (76 cases) according to the admission order and odd-even method. The control group received sufentanil analgesia, while the observation group received dexmedetomidine combined with sufentanil analgesia. The arterial blood pressure and other basic vital signs, pain score, oxidative stress index and P2X₇ receptor expression in peripheral blood mononuclear cells were compared between the two groups before and after the treatment. Results SBP, DBP and HR in the two groups were significantly decreased before and after intervention (P<0.05), but only SBP and DBP had significant differences between the two groups (P<0.05), while the difference between HR and SpO₂ was not statistically significant (P>0.05). The pain scores of all periods decreased significantly (all P<0.05), and the scores in the observation group was significantly lower than those in the control group (all P<0.05). The pain scores showed a decreasing trend in each time period within the observation group and the difference was obvious (all P<0.05). The sedation scores at 20 min and 60 min after the administration were obviously different (all P<0.05), but there was no significant difference in sedation scores between the two groups at 5 min after dosing (P>0.05). In the observation group, the serum stress responses were significantly decreased (all P<0.05), but the control group was not (all P>0.05). Flow cytometry test showed that the expression of P2X₇ receptor in CD14 cells was significantly decreased in the observation group (P<0.05), not in the control group (P>0.05). Conclusion Dexmedetomidine combined with sufentanil have an obvious analgesic effect on burn patients, without inhibition of the heart function, and it can significantly reduce the stress response and the expression of P2X₇ receptor, should be clinically popularized.