This study aimed to analyze the influence of the cellular differentiation, the tumor size and the underlying hepatic condition on the enhancement pattern of hepatocellular carcinoma (HCC) on contrast-enhanced ultrasound (CEUS). 276 patients with single lesion ≤ 5 cm who underwent CEUS exam and were pathologically confirmed as HCC were retrospectively enrolled. Enhancement patterns, washout patterns, wash-in time and washout time were observed and recorded. During the arterial phase, more poorly differentiated HCCs (42.5%) and lesions > 3 cm (35.2%) performed inhomogeneous enhancement (p < 0.05). More well differentiated HCCs (63.4%) performed late washout or no washout while compared with moderately (37.8%) or poorly (24.1%) differentiated HCCs (p < 0.05). Poorly differentiated HCCs showed the shortest washout time (83.0 ± 39.8 s), moderately differentiated HCCs showed the moderate washout time (100.4 ± 52.1 s), and well differentiated HCCs showed the longest washout time (132.3 ± 54.2 s) (p < 0.05). Lesions > 3 cm (97.2 ± 51.3 s) washed out more rapidly than lesions ≤ 3 cm (113.9 ± 53.5 s) (p < 0.05). The dynamic enhancement procedure of HCC was influenced by the cellular differentiation and the tumor size. While, hepatic background showed no influence on the dynamic enhancement of HCC.