Abstract Background Ultrasound (US) imaging is known to underestimate tumor size in clinical. This study is aimed to compare the size measurements of hepatocellular carcinoma (HCC) in three US imaging modalities, i.e. two-dimensional (2D) imaging, the arterial phase (AP) and the late phase (LP) imaging of contrast-enhanced US (CEUS). Methods Fifty-eight clinically proved HCC patients were included. The 2D and CEUS imaging were performed with Siemens S2000, Philips iu22 and BioSound Twice. 2.5 mL of SonoVue® was injected for every CEUS performance. Two physicians measured the maximal longitudinal and the transverse diameters of the tumors in 2D, the AP and the LP of CEUS from one image section. The three measurements were compared by paired t test. Results The mean longitudinal diameter of HCC appeared to be maximal in the AP (4.73 ± 2.04 cm) of CEUS and minimal in the LP (3.98 ± 1.99 cm) of CEUS. The 2D diameter (4.26 ± 2.07 cm) was in the middle between two CEUS measurements. There were significant differences between any two measurements. Conclusion There is size difference between the three kinds of HCC measurement. It appeared to be maximal in the AP of CEUS and minimal in the LP. The 2D diameter was in the middle.