Objective To assess the levels of interleukin (IL)-6, IL-10, and C reactive protein (CRP) in plasma perioperatively in patients undergoing elective hepatectomy and liver radiofrequency ablation, and to explore the extent of perioperative inflammatory responses and their relationship with short-term prognosis. Methods Totally 37 patients with hepatic lesions were enrolled, including 19 patients undergoing elective hepatectomy and 18 undergoing liver radiofrequency ablation. The plasma levels of IL-6, IL-10 and CRP were detected by enzyme-linked immunosorbent assay preoperatively, immediately after surgery, and at various time points postoperatively. The dynamic changes before and after treatment were determined by non-parametric tests. The levels of perioperative inflammatory factors and prognostic indexes were compared between the 2 surgical methods. Results Significant dynamic changes were observed in the perioperative plasma levels of IL-6, IL-10, and CRP in patients undergoing hepatectomy, as well as in the levels of IL-6 and CRP in patients undergoing liver radiofrequency ablation (all P＜0.05). The levels of IL-6 at 24 and 48 h after hepatectomy, IL-10 immediately after surgery, and CRP at 24, 48, and 72 h postoperatively were significantly higher than those before surgery (all P＜0.05). After liver radiofrequency ablation, the level of IL-6 immediately after surgery was significantly higher than that before surgery (P＜0.05), while the levels of IL-10 or CRP before or after surgery were not significantly different (all P＞0.05). Compared with patients undergoing hepatectomy, the CRP level at 48 h after radiofrequency ablation was significantly lower, and the postoperative hospital stay was significantly shorter (both P＜0.05). Conclusion Postoperative systemic inflammatory response is relatively lower after liver radiofrequency ablation, which may accelerate rehabilitation.