Objective To evaluate the effects of general anesthesia combined with multimodal analgesia on perioperative stress response and organ function in patients undergoing abdominal surgery. Methods Eighty-eight patients who underwent elective abdominal surgery in Haidu Hospital of Nan’an from January 2023 to December 2025 were retrospectively selected. According to the perioperative analgesic regimen, they were divided into control group (receiving general anesthesia alone) and combination group (receiving general anesthesia plus multimodal analgesia). Perioperative stress-related indicators, including cortisol (Cor), norepinephrine (NE) and C-reactive protein (CRP), as well as hemodynamic parameters, liver function and renal function indices, were compared between the two groups. Results After surgery, Cor, NE and CRP levels increased in both groups compared with preoperative levels. However, the postoperative increases in these indicators in the combination group were significantly lower than those in the control group (all P＜0.05). Compared with the control group, patients in the combination group showed more stable heart rate and mean arterial pressure (MAP) after surgery, and the postoperative changes in liver and renal function indices were also smaller (all P＜0.05). Conclusion General anesthesia combined with multimodal analgesia can effectively reduce perioperative stress response and help maintain hemodynamic and organ function stability in patients undergoing abdominal surgery, indicating favorable clinical applicability and safety.