Objective To investigate the effect of high， middle and low dose dexmedetomidine combined with sufentanil on perioperative analgesia and sleep quality in patients with oral cancer. Methods A total of 158 patients undergoing oral cancer surgery in the hospital from January 2023 to June 2024 were selected and divided into group A［n = 53，0.6 μg/（kg·h） dexmedetomidine + 2 μg/kg sufentanil］and group B［n = 53，0.4 μg/（kg·h） dexmedetomidine + 2 μg/kg sufentanil］ ， Group C ［n = 52， 0.2 μg/（kg·h） dexmedetomidine + 2 μg/kg sufentanil］by random number table method. Stress response indexes ［brain-derived neurotrophic factor （BDNF）， cortisol （Cor）， interleukin-6 （IL-6）］， bifrequency index and analgcsia nociccption index（BIS， ANI）， pain level， T lymphocyte subsets CD3⁺， CD4⁺， CD8⁺ levels， Richards Campbell Sleep Scale （RCSQ） score and adverse reactions were compared between the two groups. Results Compared with 12 h before surgery， serum levels of BDNF， Cor and IL-6 in 3 groups were decreased 48 h after surgery， group A was lower than group B， group C， group B was lower than group C（P < 0.05）. Compared with T₀， BIS at T₁ ~ T₃ were significantly different between the 3 groups （P < 0.05）， BIS at T₁ ~ T₃ were lower than those at T₀ （P < 0.05）， and there was no significant difference in BIS at the same time between the 3 groups （P>0.05）， from T₁ to T₃， ANI was higher than that at T₀， and ANI in group A was higher than that in group B and group C （P < 0.05）. Compared with the preoperative results， the pain scores of the 3 groups were decreased at 1 h， 6 h， 24 h and 48 h after operation， and the pain scores of group A were lower than those of group B and C， and the pain scores of group B were lower than those of group C （P < 0.05）. After operation， CD3⁺ and CD4⁺ were decreased in all 3 groups， group A was lower than group B and group C， group B was lower than group C （P < 0.05）， and CD8⁺ was increased in all 3 groups， group A was higher than group B and group C， group B was higher than group C （P < 0.05）. Compared with 1 day before the operation， the sleep quality scores of the three groups on the night after the operation and the second night after the operation were all decreased， group A was lower than group B and group C， and group B was lower than group C（P < 0.05）. The incidence of hypotension and sinus bradycardia in group A was higher than that in group B and group C （P < 0.05）. There was no significant difference in the incidence of hypotension and sinus bradycardia between group B and group C （P > 0.05）. There was no significant difference in the incidence of nausea， vomiting and dizziness among the three groups （P > 0.05）. Conclusion The analgesic effect of 0.6 μg/（kg·h） dose dexmedetomidine combined with sufentanil can effectively reduce the body's stress response and immune suppression， improve sleep quality， but with a greater incidence of intraoperative hypotension and bradycardia.