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Objective To explore the application value of retrobulbar nerve block combined with general anesthesia in the penetrating keratoplasty (PKP). Methods A total of 100 recipients undergoing PKP from January 2017 to January 2019 were recruited in this study. All recipients were divided into the observation group (n=50) and control group (n=50) by random number table method. In the control group, patients received laryngeal mask airway under general anesthesia, and in the observation group, patients received laryngeal mask airway under general anesthesia combined with retrobulbar nerve block. Hemodynamic changes of the PKP recipients before and after operation were observed in two groups. The dosage of analgesic drugs and the incidence of complications were observed in two groups. The degree of pain at postoperative 2-, 6- and 24-h was evaluated by visual analogue scale (VAS) in two groups. The awakening situation of the recipients in two groups was observed. The levels of inflammatory cytokines at 1 d before and after operation were statistically compared in two groups. Results The average arterial pressure and heart rate at intraoperative 15 min and after the surgery in the observation group were significantly higher than those in the control group (both P < 0.05). In the observation group, the dosage of remifentanil and propofol were (1.0±0.4) mg and (299±40) mg, significantly lower than (1.3±0.6) mg and (365±42) mg in the control group (both P < 0.05). The incidence of complications did not significantly differ between two groups (P > 0.05). In the observation group, the VAS scores at 2-, 6- and 12-h after operation were remarkably lower than those in the control group (all P < 0.01). The respiratory recovery time, eye opening time, directional force recovery time and extubation time of the recipients in the observation group were significantly shorter than those in the control group (all P < 0.05). The expression levels of including interleukin (IL)-1, IL-6 and tumor necrosis factor-α (TNF-α) at postoperative 1 d in the observation group were considerably lower than those in the control group (all P < 0.05). Conclusions Retrobulbar nerve block combined with general anesthesia can maintain hemodynamic stability during PKP, reduce the dosage of remifentanil and propofol and alleviate the degree of postoperative pain and inflammatory responses of the recipients.