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Background: This study aims to explore the analgesic effect of lidocaine administered through the hepatic artery during hepatic artery infusion chemotherapy (HAIC) for hepatocellular carcinoma (HCC)., Methods: A total of 45 HCC patients were randomly divided into a study group and a control group. Both groups received oxaliplatin (OXA) based FOLFOX protocol via electronic infusion pump. The study group was continuously infused with 100 mg of lidocaine during HAIC, while 5% glucose solution was infused in the same way as described above. Changes in vital signs, visual analogue score (VAS) and general comfort score (GCQ scale) were recorded before surgery (Time point 0), at the end of infusion (Time point 01), 1 h after HAIC (Time point 02), 3 h after HAIC (Time point 03) and 6 h after HAIC (Time point 04)., Results: At each point of time from Time point 0 through Time point 04, the differences in MAP, RR and SPO 2 between the two groups were not statistically significant ( P  > 0.05). At each point of time from Time point 01 through Time point 04, the mean VAS scores in the study group were smaller and GCQ scores were higher than those in the control group, and the differences were both statistically significant ( P  < 0.05)., Conclusions: Lidocaine infusion through the hepatic artery during HAIC effectively reduces intraoperative and postoperative pain and improves patient satisfaction with pain management, making it a valuable technique for clinical practice., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Zhang, Liao, Yang, Tian, Wu, Zeng, He, Zhang, Wei and Liu.)