〔Abstract〕 Objective To investigate the effect of ultrasound-guided thoracic paravertebral block (TPVB) combined with general anesthesia on postoperative cognitive function of patients undergoing modified radical mastectomy. Methods A total of 56 patients with modified radical mastectomy admitted to Xinyang Central Hospital from January 2020 to December 2021 were divided into an observation group (under ultrasound guidance TPVB combined with general anesthesia) and a control group (general anesthesia) by random number table method, with 28 cases in each group. The hemodynamic changes of the two groups were compared before anesthesia (T0), at the time of skin incision (T1), 60 min at the beginning of surgery (T2), and at the end of surgery (T3). The amount of anesthetic drugs in the two groups was recorded during the surgery, and the neurological function of the two groups was recorded before and 1 day after surgery. The incidence of postoperative adverse reactions was compared between the two groups. Results There was no significant difference in mean arterial pressure (MAP) and heart rate (HR) between T1 ~ T3 and T0 (P > 0.05). MAP and HR of the control group at T1 ~ T3 were higher than T0, and the differences were statistically significant (P < 0.05). MAP and HR in the observation group were lower than those in the control group from T1 ~ T3, and the differences were statistically significant (P < 0.05). The intraoperative dosage of propofol and remifentanil in the observation group was lower than that in the control group, and the difference was statistically significant (P < 0.05). After surgery, the scores of the mini-mental state examination (MMSE) in the two groups were lower than those before surgery 1 day, and the MMSE score in the observation group was higher than that in the control group at the same time 1 day after surgery, the differences were statistically significant (P < 0.05). The incidence of postoperative adverse reactions in the observation group was lower than that in the control group, and the difference was statistically significant (P < 0.05). Conclusion Ultrasound-guided TPVB combined general anesthesia in modified radical mastectomy can maintain the hemodynamic stability of patients, reduce the amount of anesthesia drugs, improve postoperative cognitive function and reduce postoperative complications.