Objective To investigate the effects of patient-controlled analgesia combined with epidural anesthesia on hemodynamics and immune stress response in patients undergoing surgery for high complex anal fistula.Methods A total of 120 patients with high complex anal fistula who underwent surgery in our hospital from February 2017 to July 2021 were included in the study. They were randomly divided into control group (60 cases) and study group (60 cases). The control group received combined spinal and epidural anesthesia, and the study group received patient-controlled analgesia combined with epidural anesthesia. The anesthetic effect, analgesic effect, hemodynamics, immune function and stress response were compared between the two groups.Results The onset time of anesthesia in the study group was longer than that in the control group, and the duration of analgesia and the time spent in post-anesthesia care unit were shorter in the study group than those in the control group (P > 0.05). The Visual Analogue Scale (VAS) and Bruggrmann Comfort Scale (BCS) scores of the study group and the control group were compared at 6 h, 12 h, 24 h and 48 h after the operation, and the results demonstrated that: ①There were differences in VAS and BCS scores at different time points (F = 14.105 and 7.148, both P < 0.001); ②There were differences in VAS and BCS scores between the study group and the control group (F = 9.485 and 8.151, both P < 0.001); ③The change trend of VAS and BCS scores was different between the study group and the control group (F = 6.841, 7.246, both P < 0.001). The mean arterial pressure (MAP), heart rate (HR) and oxyhemoglobin saturation (SpO₂) of the study group were compared with those of the control group before anesthesia, 10 min after anesthesia, 30 min after anesthesia and at the end of operation, and the results demonstrated that: ①There were differences in MAP, HR and SpO₂ at different time points (F = 9.662, 10.125 and 11.346, all P < 0.001); ②There were differences in MAP, HR and SpO₂ between the study group and the control group (F = 7.434, 7.589 and 9.561, all P < 0.001); ③The change trend of MAP, HR and SpO₂ was different between the study group and the control group (F = 7.581, 6.976 and 10.678, all P < 0.001). The serum growth hormone (GH), cortisol (Cor), angiotensin Ⅱ (Ang Ⅱ) and adrenaline (AD) in the study group were compared with those in the control group before the induction of anesthesia, 30 minutes after anesthesia and 24 hours after operation, and the results demonstrated that: ①There were differences in AD, GH, Ang Ⅱ and Cor at different time points (F = 10.718, 10.359, 12.560 and 9.923, all P < 0.001); ②There were differences in AD, GH, Ang Ⅱ and Cor between the study group and the control group (F = 8.327, 10.597, 11.676, 8.782, all P < 0.001); ③The change trend of AD, GH, Ang Ⅱ and Cor was different between the study group and the control group (F = 7.733, 8.911, 10.824, 9.823, all P < 0.001). In addition, the levels of CD4⁺ and CD8⁺ cells as well as the CD4⁺/CD8⁺ ratio were compared between the study group and the control group before the induction of anesthesia, 30 minutes after anesthesia and 24 hours after operation, and the results demonstrated that: ①There were differences in the levels of CD4⁺ cells and the CD4⁺/CD8⁺ ratio at different time points (F = 8.852 and 11.980, both P < 0.001); ②There were differences in the levels of CD4⁺ cells and the CD4⁺/CD8⁺ ratio between the study group and the control group (F = 7.473 and 10.534, both P < 0.001); ③The change trend of the levels of CD4⁺ cells and the CD4⁺/CD8⁺ ratio was different between the study group and the control group (F = 7.470 and 10.178, both P < 0.001).Conclusions Patient-controlled analgesia combined with epidural anesthesia is effective in the surgery for high complex anal fistula. It can ameliorate the stress response, promote the stability of hemodynamics, and reduce the immunosuppressive effect of anesthesia to a certain extent.