Objective Comparison of the value of Sonazoid and SonoVue in ultrasound guided microwave ablation of small hepatocellular carcinoma. Methods The clinical data of patients with small hepatocellular carcinoma treated by ultrasound guided percutaneous microwave ablation from January 2021 to December 2022 in Hangzhou Xixi Hospital affiliated to Zhejiang University School of Medicine were retrospectively analyzed. The patients were divided into Sonazoid group and SonoVue group according to the different contrast media used during the operation. Both groups of patients underwent CEUS to make the tumor clear before puncture. Make a 5-point difficulty table for the puncture process and compare the puncture difficulty of the two groups of cases. Contrast-enhanced imaging（CEMRI、CECT or CEUS） was performed within 3 months after ablation to evaluate the short-term efficacy. Results Finally,67 patients were included in the study. Of the 25 patients in the Sonazoid group, the age ranged from 41 to 82 (60.64 ± 9.46) years, and the tumor size ranged from 1.1 to 2.8 (1.78 ± 0.45) cm. Of the 42 patients in the SonoVue group, the age ranged from 38 to 78 (62.26 ± 9.27) years, and the tumor size ranged from 1.1 to 3.0 (1.89 ± 0.49) cm. There was no significant difference in age and tumor size between the two groups (P>0.05). The score of puncture difficulty was ranged from 2.0 to 2.7 (2.28 ± 0.29) points in Sonazoid group and ranged from 2.0 to 4.7 (2.95 ± 0.85) points in SonoVue group. The difference between the two groups was significant (P<0.05). The results of Contrast-enhanced imaging examination within 3 months after ablation showed that the complete ablation rate in Sonazoid group was 100% (25/25), and in SonoVue group was 95.2% (40/42). There was no statistically significant difference between the two groups (P>0.05). Conclusion CEUS is beneficial for puncture before ablation of small hepatocellular carcinoma that is not clearly visualized on gray-scale ultrasound. In the post-vascular phase of Sonazoid, tumors can be clearly visualized for a long time. This allows surgeons to continuously operate and accurately puncture, and reduces the difficulty of puncture. It is possible to achieve better ablation effects.