Objective To determine the value of contrast-enhanced ultrasound (CEUS) in the differentiation of primary liver cancer (PLC) and hepatic alveolar echinococcosis (HAE). Methods The data of 56 patients with PLC or HAE were collected between January 2010 and May 2015. Grayscale and CEUS features of the patients were analyzed retrospectively. The frequency of each imaging finding, including calcification, arterial enhancement, and internal enhancement were evaluated and compared. Results Statistically significant difference of the proportion of gender and age were detected between the two groups (P=0.013, 0.002). Thirty-eight PLC lesions were detected in 32 patients. The diameters of PLC lesions were 3-10 cm with an average of (5.6±2.1) cm. Thirty-two HAE lesions were found in 24 patients. The diameters of HAE lesions were 4-12 cm with an average of (9.1±4.4) cm. Statistically significant difference of lesion size and the incidence rate of calcification (5.3% vs. 75.0%) were seen between PLC and HAE (P<0.001). Peripheral enhancement were seen in 100.0% (38/38) PLC lesions, including 84.2% (32/38) hyperenhancement and 15.8% (6/38) dendritic hyperenhancement. All PLC lesions demonstrated hypoenhancement in late phase. Irregular peripherally hyperenhancement both in arterial and late phase were detected in 43.8% (14/32) HAE lesions. The other 56.2% (18/32) HAE lesions showed no peripheral enhancement both in arterial and late phase. No internal enhancement were seen in HAE lesions. The presence of arterial enhancement (100.0% vs. 43.8%) and absence of internal enhancement (0 vs. 100.0%) were significantly different between PLC and HAE (P<0.001). Conclusions PLC is predicted by arterial phase hyperenhancement and late phase hypoenhancement on CEUS. HAE is predicted with calcification on baseline sonography and internal non-enhancement on CEUS. Arterial phase enhancement is less common and less intensive in HAE than in PLC which also contributes to the differentiation of these lesions.