To analyze the effects of dexmedetomidine combined with transverse abdominal muscle plane (TAP) block during hysteromyoma surgery of patients on their stress response and alert-sedation scale (OAAS) score. Methods: 110 patients who wanted hysteromyoma surgery selected and were randomly divided into two groups (55 patients in each group) from October 2021 to September 2022. The patients in the group A were treated with TAP block anesthesia, and the patients in the group B were treated with dexmedetomidine combined with TAP block anesthesia. The degree of postoperative pain evaluated by VAS score, the number of pressing analgesia pump, the stress response, the state of consciousness evaluated by OAAS score, the cognitive function evaluated by MMSE score, and the adverse reactions situation of the patients were compared between the two groups. Results: The VAS score of the patients in group B at each time point after surgery was significantly lower than that of the patients in group A, and the number of analgesic pump compression of the patients in group B was significantly less. The levels of serum norepinephrine (318.20±23.45 ng/L), cortisol (162.33±37.03 ng/L), and cardiac natriuretic hormone (0.33±0.03 nmol/L) of the patients in group B were significantly lower than those (345.48±25.33 ng/L, 181.36±40.04) ng/L, and 0.36±0.04 nmol/L) of the patients in group A. The OAAS score of the patients in group B at extubation or at 1h after extubation were significantly higher than that of the patients in group A. The MMSE score (26.20±0.94 points) of the patients in group B in 1 day after surgery was significantly higher than that (25.38±1.02 points) of the patients in group A (all P<0.05). The incidence of adverse reactions (14.6%) of the patients in group B had no significant different from that (12.7%) of the patients in group A (P>0.05). Conclusion: The application of dexmedetomidine combined with TAP block in the hysteromyoma surgery of the patients has better effect, which relieves postoperative pain and stress reaction, and has a slight impact on the consciousness and the cognitive function of the patient, with good medication safety.