Objective: To explore the molecular of the interaction between hepatocellular carcinoma (HCC) markers, glypican-3(GPC3) and miR-202 . Methods:126 cases of Clinical HCC tissue samples and serum samples were collected. The expression of GPC3 was detected by immunohistochemistry, and the level of circulating miR-202 was detected by qRt-PCR . The HepG2 cells were cultured and transfected with mir-202 mimics, the expression of mir-202 was detected by qrt-pcr, and the expression of GPC3 was detected by Westem Blotting. The effect of mir-202 mimics on the proliferation activity of HepG2 cells was detected by CCK8 assay. Luciferase reporter gene was used to determine the regulation of mir-202 on GPC3. Results:The total positive rate of GPC3 in 126 cases of HCC was 77.78%. Its expression level was not related to the patient’s gender, age, tumor size and clinical stage, but was highly correlated with the type of histological differentiation and microvascular invasion . The circulating miR-202 in HCC patients was at a low level, and was inversely correlated with the expression level of GPC3 in cancer tissues. The expression of miR-202 was up-regulated in HepG2 cells, and the expression of GPC3 was down-regulated accordingly, and the proliferation activity of cancer cells was thus inhibited. Luciferase experiment confirmed that miR-202 could directly and negatively regulate the expression of GPC3. Conclusions: High expression of GPC3 is a sign of malignant biological feature of HCC and may predict a poor prognosis. This study is the first to demonstrate that GPC3 is directly regulated by miR-202 . We believe that an targeted GPC3 therapeutic strategy, if it can assist to improve the function of miR-202 ,may produce a synergistic ant-tumor effect for HCG.