Objective To explore the value of quantitative parameters from contrast-enhanced ultrasound(CEUS) combined with alpha-fetoprotein (AFP)、protein induced by vitamin K absence or antagonist-Ⅱ (PIVKA-Ⅱ )、α-L-fucosidase (AFU) from serum in the early diagnosis of liver cancer with cirrhosis. Methods From July 2018 to March 2021, 156 patients diagnosed with liver cirrhosis in our hospital were selected as the liver cancer group, and a total of 70 healthy volunteers who underwent physical examination in our hospital during the same period were selected as the normal control group. Quantitative parameters of CEUS [enhancement time(ET),time to peak(TTP), washtime(WT),peak intensity (PI)] and serum markers(AFP、PIVKA-Ⅱ、AFU)were compared between the two groups. ROC curve was used to evaluate the diagnostic efficacy of CEUS quantitative parameters ET,TTP,WT and PI and serum markers AFP、PIVKA-Ⅱand AFU alone and in combination for liver cancer with cirrhosis. Results The value of ET,TTP,WT of hepatocellular carcinoma group was shorter than that of normal control group, and the PI value was higher than that of normal control group. The difference had statistical sense（P＜0.05）.The levels of AFP, PIVKA-Ⅱ and AFU in hepatocellular carcinoma group were higher than those in normal control group. Difference between the two groups had statistical significance(P＜0.05).The sensitivity,positive prediction rate and AUC value of PIVKA-Ⅱ were the highest when each index was detected separately for the diagnosis of liver cancer with cirrhosis. The sensitivity, specificity, positive prediction rate and negative prediction rate of ET+TTP+WT+PI+AFP+ PIVKA-Ⅱ +AFU were the highest in combined diagnosis.The differences were statistically significant(P＜0.05).Conclusion The combination of quantitative parameters of CEUS with AFP, PIVKA-Ⅱ and AFU of serum is of great value for the early diagnosis of liver cancer with cirrhosis.