Objective To analyze the effect of ultrasound-guided nerve block combined with general anesthesia on analgesia and hemodynamics in patients with total knee replacement. Methods A total of 80 patients with total knee replacement treated in Longyan First Hospital Affiliated to Fujian Medical University from January 2019 to June 2021 were selected as the research objects. They were divided into control group (n=40) and observation group (n=40) by random number table method. The control group were treated with general anesthesia, and the observation group were treated with ultrasound-guided lumbar plexus sciatic nerve block combined with general anesthesia. The visual analogue scale (VAS) score, analgesic situation, anesthetic dosage and hemodynamic changes were compared between the two groups. Results The heart rate and mean artery pressure of the observation group during intubation and extubation were higher than those of the control group, the differences were statistically significant (P<0.05). The VAS score of the observation group was lower than that of the control group, the time from the first demand for patient-controlled analgesia pump (PCA) to conscious extubation was longer than that of the control group, the recovery time of anesthesia was shorter than that of the control group, the pressing times of analgesia pump and the use of Sufentanil within 24 hours after operation were less than those of the control group, and the score of patients' satisfaction with analgesia was higher than that of the control group, the differences were statistically significant (P<0.05). The doses of Propofol, Remifentanil and Sufentanil in the observation group were lower than those in the control group, the differences were statistically significant (P<0.05). There was no significant difference in anesthesia time between the two groups (P＞0.05). The recovery time and extubation time of the observation group were shorter than those of the control group, the differences were statistically significcant (P<0.05). Conclusion Using ultrasound-guided nerve block combined with general anesthesia can maintain stable hemodynamics and have good analgesic effect. It can effectively reduce patients' pain and reduce the dosage of narcotic analgesics. It has high application value.