Objective: To study the role of remifentanil in improving coagulation function by regulating the inflammatory response mediated by the NF-κB signaling pathway in adult cardiopulmonary bypass cardiac surgery. Methods: The research subjects were 204 adult patients who underwent cardiopulmonary bypass cardiac surgery. They were divided into two groups based on different intervention methods. The patients in the study group received targeted remifentanil infusion anesthesia, while those in the control group received intermittent sufentanil infusion anesthesia. The differences in hemodynamic indicators, surgical indicators, inflammatory response, stress response, coagulation function, NF-κB signaling pathway activity, and complications were compared between the two groups. Results: The differences in heart rate (HR), mean arterial pressure (MAP), central venous pressure (CVP), cardiac contractility index (CCI), stroke volume variation (SVV), pulmonary artery pressure (PAP), peripheral capillary oxygen saturation (SpO?), and bispectral index (BIS) at different time points between the two groups were statistically significant (P 0.05). Conclusion: Remifentanil regulates the NF-κB signaling pathway by modulating the expression of P65, P50, Act1, and IκBα proteins, thereby reducing the release of inflammatory factors and improving coagulation function. This demonstrates the advantages of remifentanil not only in analgesia but also in its significant role in postoperative immune regulation and recovery of coagulation function.