By prediction from chip assay and identification from a series of biological experiments, we demonstrated the deregulation of C1QTNF1-AS1, miR-221-3p and SOCS3 in HCC tissues and revealed the physical binding between C1QTNF1-AS1/miR-221-3p and miR-221-3p/SOCS3. Here, SOCS3 is linked to hepatocellular carcinoma.