This study explored the effect of pain sensitivity on the application of opioid-free anesthesia (OFA) in laparoscopic cholecystectomy (LC). Fifty-nine patients who accepted LC in the First People's Hospital of Huai'an City from May 2023 to October 2023 were included. Pain sensitivity questionnaire (PSQ) was used for evaluating patients' pain sensitivity before surgery. The results suggested that preoperative PSQ score was positively linked to postoperative VAS pain score at each time point, among which patients with high pain sensitivity had more intraoperative blood pressure fluctuations, higher incidence of postoperative acute pain, more times of remedial analgesia, significantly decreased satisfaction with pain management, and higher VAS score at all time points following surgery than patients with low pain sensitivity. We conclude that pain sensitivity can affect the effectiveness of OFA in LC. Patients with high pain sensitivity have a higher risk of postoperative acute pain and are not suitable for OFA.