〔Abstract〕 Objective To explore the clinical value of contrast-enhanced ultrasonography (CEUS) in differential diagnosis of primary small hepatocellular carcinoma and regenerative nodules of cirrhosis. Methods A total of 40 patients with small primary liver cancer and 40 patients with regenerative nodules of cirrhosis admitted to Mengchao Hepatobiliary Hospital of Fujian Medical University from January 2019 to December 2021 were selected. All patients received CEUS examination, and the diagnostic efficacy of CEUS for small primary liver cancer was calculated based on pathological results. The time-intensity curves of CEUS in the two groups were analyzed, and the characteristics of CEUS sonogram were compared. Results According to the pathological results as the gold standard, there were 40 cases of primary small liver cancer (44 lesions) and 40 cases of liver cirrhosis regenerative nodules (49 lesions). The positive predictive value, negative predictive value, sensitivity, specificity and accuracy of 40 cases of small primary liver cancer detected by CEUS were 95.23%, 92.16%, 90.91%, 95.92% and 93.55%, respectively. The peak time and enhancement time of primary small liver cancer group were shorter than those of the liver cirrhosis regenerative nodules group, and the peak intensity and enhancement slope were higher than those of the liver cirrhosis regenerative nodules group, the differences were statistically significant (P < 0.05). There were statistically significant differences in the proportion of high, equal and low enhancement in arterial phase between the two groups (P < 0.05). However, there were statistically significant differences in the proportion of equal and low enhancement in portal phase and delay phase (P < 0.05). Conclusion CEUS has high diagnostic efficiency for primary small hepatocellular carcinoma, and can effectively differentiate primary small hepatocellular carcinoma from regenerative nodules of cirrhosis according to CEUS characteristics, time-intensity curve and its parameters.