Abstract: Objective To compare the effect of surgical resection (SR) and radiofrequency ablation (RFA) for multiple HCC within the Milan criteria. Methods Clinical data about 140 patients with well-preserved liver function and multinodular HCC within the Milan criteria who received surgical resection (n=78) or RFA (n=62) as initial treatment were retrospectively analyzed. The postoperative complications, liver function and survival data were analyzed and compared. Results The incidences of seroperitoneum, anemia and hypoproteinemia were significantly higher in SR group than RFA group; The levels of postoperative ALT and AST were higher in SR group on the third day after surgery than RFA group; the 1-, 2-, 3-year overall survival rates were 80.8%, 60.3%, 48.7% respectively in SR group and 83.9%, 48.0%, 30.6% respectively in RFA group (P=0.037); the 1-, 2-, 3-year recurrence-free survival rates were 74.4%, 47.4%, 37.2% respectively in SR group and 71.0%, 38.7%, 21.0% respectively in RFA group (P=0.007). Conclusion For patients with multiple HCC and Child-pugh A liver function, surgical resection may still be an optimal choice when tumors within Milan criteria.