Objective: To investigate the efficacy of microwave ablation in the treatment of hepatocellular carcinoma (HCC) within the Milan criteria and to investigate the differences in clinical efficacy of microwave ablation in tumors with different sizes. Methods: A retrospective analysis was performed on the clinical data of the patients with HCC within the Milan criteria who received microwave ablation in our hospital from January 2011 to January 2013. The complete ablation rate, incidence rate of major complications, recurrence rate, and overall survival rate were analyzed and the treatment outcomes were compared between two groups with different tumors sizes. The patients were followed up for 3.4-61.8 months. The Kaplan-Meier method was used to calculate overall survival rate, local recurrence rate, and distant recurrence rate. Comparison of rates between groups was made by the chi-square test and comparison of survival rates between groups was made by the log-rank test. Results: A total of 696 patients with HCC within the Milan criteria involving 801 tumors were included in this study. The complete ablation rate was 93.8% (653/696) and the incidence rate of major complications was 1.7% (12/696). The median survival time was 59.6 months and the 1-, 2-, and 3-year overall survival rates were 94.8%, 82.2%, and 71.7%, respectively. The local recurrence rate was 13.4% (93/696) and the rate of intrahepatic distant metastasis was 40.1% (279/696). The overall intrahepatic recurrence rate was 48.1% (335/696), and the 1-, 2-, and 3-year recurrence rates were 22.9%, 38.4%, and 46.8%, respectively. There were no significant differences in complete ablation rate, incidence rate of major complications, and overall survival rate between the two groups with different tumor sizes (diameters≤3 cm and 3-5 cm) (P = 0.12; P = 0.61; P = 0.61). Conclusion Microwave ablation is a safe and effective treatment modality for HCC within the Milan criteria. And there are no significant differences in safety, effectiveness, and long-term efficacy of microwave ablation between the two groups with different tumor sizes (diameters ≤3 cm and 3-5 cm). However, if the operator’s experience is not rich and cannot accurately use conformal ablation and make an individualized treatment, the tumors with a diameter of 3-5 cm should be carefully treated using microwave ablation to avoid residual tumor after treatment.