Abstract: Objective To discuss the clinical value of miR-224 in the diagnosis of HCC at early stage. Methods Two cohorts of 335 subjects,including early-stage HCC,liver cirrhosis(LC),chronic hepatitis B(CHB) and healthy controls(HC),were enrolled,and the area under the curve(AUC) were calculated for miR-224 alone or in combination with AFP to evaluate the sensitivity and specificity in diagnosing HCC at early stage. Results The serum miR-224 in early-stage of HCC patients increased significantly as compared with LC,CHB and HC patients,however,it decreased significantly after surgical treatment;the serum miR-224 was positively correlated with that in the tumor tissue.ROC analysis demonstrated that the AUC for serum miR-224 was 0.880(95%CI:0.838-0.923;sensitivity was 86.5%,specificity was 76.7%) in discriminating early-stage HCC from all controls(LC,CHB and healthy controls),higher than that for AFP(AUC=0.700,95%CI:0.633-0.767;sensitivity was 71.9%,specificity was 63.7%),P<0.01.Moreover,serum miR-224 still had a better performance than AFP in discriminating HCC from the disease controls including LC and CHB,or from either of the both.When two markers(miR-224 and AFP) were used together,the diagnostic accuracy increased significantly as compared with either marker alone. Conclusion The serum miR-224 is a potential biomarker for detecting early-stage HCC,with better performance than AFP,and correlates positively with that in the tumor tissues,thus probably reflecting the development and progression of HCC.