Abstract: Objective To investigate the difference of ultrasound and detection of two D-dimer, AFP-L3 levels on the diagnostic accuracy of primary hepatocellular carcinoma. Methods 50 cases of primary liver cancer patients were performed contrast enhanced ultrasound examination, the D-dimer and AFP-L3 levels in patient were detected. Results The diagnostic rate of primary hepatocellular carcinoma with Ultrasound, D-dimer and AFP-L were 76%, 54% and 74% respectively. The AFP-L3 level and ultrasound diagnosis had higher detection rate but no significantly difference between these three methods (P>0.05). The sensitivity and specificity of combined ultrasound, D-dimer and AFP-L3 levels detection in the diagnosis of primary hepatocellular carcinoma were higher than any single method (P<0.05). Conclusion The ultrasound and AFP-L3 level detection may be prefer method in clinic, and combined ultrasound with D-dimer and AFP-L3 level detection might improve the early diagnosis rate of primary liver cancer.