This research aims to investigate the effect of ultrasound-guided continuous thoracic paravertebral nerve block in patients undergoing radical mastectomy. Ninety-six patients who underwent radical mastectomy were equally divided into a study group (administered with a continuous thoracic paravertebral nerve block and general anesthesia) and a control group (given conventional general anesthesia) with a random number table. At T2–T4 (T2: immediate tracheal intubation; T3: at skin incision; T4: at extubation), mean artery pressure (MAP) and hear rate (HR) were significantly lower in the study group (p < 0.05); however, there was no significant difference in blood oxygen saturation (SpO2) between the two groups at different time points. At T2–T4, cortisol (Cor) levels were significantly lower in the study group (p < 0.05). At T0–T2, there was no significant difference in the levels of adrenocorticotropic hormone (ACTH) between the two groups. At T3–T4, the levels of ACTH in the study group were significantly lower (p < 0.05). There were no significant differences in blood pressure between the two groups at any time point. At the moment of discharge from the resuscitation room and 2 hours after surgery, the numerical rating scale (NRS) score in the study group was significantly reduced (p < 0.05). The incidence of adverse reactions in the study group was 10.42%; this was lower than that in the control group (33.33%) (p < 0.05). Finally, the use of fentanyl and propofol, and the frequency of analgesic pump use, were significantly lower in the study group (p < 0.05). Ultrasound-guided thoracic paravertebral nerve block can effectively maintain hemodynamic stability, improve the stress response, reduce postoperative pain, reduce the use of anesthetic drugs, and effectively control the incidence of adverse reactions in patients undergoing radical mastectomy.