Objective：This study aims to explore the molecular mechanism of the interaction between hepatocellular carcinoma（HCC） markers of glypican-3（GPC3）and miR-202. Methods：Total 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 protein was detected by Western blot. 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. Conclusion：This study demonstrates that GPC3 is directly regulated by miR-202，and high expression of GPC3 is a sign of malignant biological feature of HCC. Any targeted GPC3 therapeutic strategy，if it can assist to improve the function of miR-202，may produce a synergistic anti-tumor effect for HCC.