Objective: To compare the effect of dynamic three-dimensional contrast-enhanced ultrasound (D-3D-CEUS) and enhanced CT (CECT) in the diagnosis of hepatocellular carcinoma and the evaluation of therapeutic effect after microwave ablation, and to explore the effect of both in the diagnosis and evaluation of therapeutic effect of hepatocellular carcinoma. Methods: 80 patients with hepatocellular carcinoma underwent microwave ablation in our hospital from October 2017 to January 2019 were selected. All patients were inspected by D-3D-CEUS and CECT. The diagnosis, the internal display of the arterial phase tumor, the blood supply vessels of the tumor and the tumor boundary of hepatocellular carcinoma of the two methods were compared. All patients were followed up for one year, based on the final results of clinical follow-up as the gold standard, the evaluation and diagnostic efficacy of microwave ablation for hepatocellular carcinoma were evaluated. Results: 80 patients were diagnosed as hepatocellular carcinoma by D-3D-CEUS, among them, there were 55 cases with the diameter of hepatocellular carcinoma <3cm, and 25 cases with the diameter of hepatocellular carcinoma ≥ 3cm, 21 cases with internal necrosis, there were no statistically significant differences between the two in the diagnostic efficacy of diameter and internal necrosis in hepatocellular carcinoma (P>0.05). The clarity of D-3D-CEUS in the blood supply vessels of hepatocellular carcinoma was better than that of CECT, and the clarity of tumor boundary of CECT was better than that of D-3D-CEUS, which had showed a statistical difference (P<0.05). There was no statistical difference between the two groups in the internal display of arterial tumors (P>0.05). After clinical follow-up, 11 patients were finally diagnosed as local residual, 69 patients were completely ablated, the accuracy rate of D-3D-CEUS efficacy evaluation was 91.25% (73/80), the accuracy rate of CECT efficacy evaluation was 90.00% (72/80), there was no statistical difference in the accuracy of the two methods (P>0.05). The sensitivity, specificity, negative predictive value and positive predictive value of D-3D-CEUS and CECT were 94.20%, 91.30%, 72.73%, 81.82%, 66.67%, 60.00%, 95.59% and 96.92% respectively. There were no significant differences in the sensitivity, specificity, negative predictive value and positive predictive value between the two methods (P>0.05).Conclusion: D-3D-CEUS is superior to CECT in the clarity of blood supply vessels of hepatocellular carcinoma, and CECT is superior to D-3D-CEUS in the clarity of tumor boundary. Both of them have good effect on the efficacy evaluation of hepatocellular carcinoma after microwave ablation.