Background Radiofrequency ablation (RFA) is a minimally invasive and effective method for local tumor destruction in nonsurgical patients with early-stage hepatocellular carcinoma (HCC). General anesthesia (GA) has been used for RFA. GA can decrease the hepatic blood flow and cause more hepatic dysfunction. This study aimed to compare the hemodynamic response, recovery characteristics, and postprocedural analgesia after induction of GA with either sevoflurane–propofol or sevoflurane–ketofol in liver patients undergoing RFA of HCC. Patients and methods Eighty patients with hepatic cirrhosis scheduled for RFA of HCC were randomly allocated into two groups. In group PS, induction of anesthesia was achieved using sevoflurane with propofol (1%). In group KPS, induction of anesthesia was achieved using sevoflurane with ketofol (prepared at a ratio of 1: 2). Results Regarding the induction time, the laryngeal mask airway (LMA) insertion time, the percentage of LMA insertions from the first attempt, time to removal of LMA, and time to emergence were comparable between the two groups. However, the rescue analgesia time was longer in group KPS compared with group PS ( P < 0.001). The number of episodes during which blood pressure was below 20% of baseline blood pressure, as well as the highest and the lowest mean arterial pressure, was comparable between the two groups. Postoperative levels of liver enzymes were comparable between the two groups. In the recovery unit, only one patient (2.5%) in group KPS suffered from postoperative emergence agitation, and three patients (7.5%) suffered from nausea. Conclusion Either sevoflurane–propofol or sevoflurane–ketofol may be used as alternatives in liver patients undergoing RFA of HCC as both techniques have favorable anesthetic profiles and provide hemodynamic stability. However, when choosing sevoflurane–ketofol, the advantage of its enhanced analgesic effect must be weighed against the increased risk for postoperative nausea and vomiting.