Objective: lncRNA HAND2 antisense RNA 1 (HAND2-AS1) is consistently well recognized to suppress multiple tumors, while its function was uncertified in liver cancer. Materials and Methods: qRT-PCR analysis and TCGA database discovered the expression in liver cancer. CCK-8 and Transwell migration assay demonstrated the impact of HAND2-AS1 on cell proliferation and migration. Bioinformatic analysis and luciferase reporter assay were utilized to monitor the binding between HAND2-AS1 or SOCS5 mRNA and miR-3118. The function of SOCS5 on inactivating the JAK-STAT pathway was confirmed through Western blot assays. Rescue experiments unmasked that HAND2-AS1-mediated SOCS5 affected cell proliferation and migration through the JAK-STAT pathway in liver cancer. Results: The authors discovered the downregulated HAND2-AS1 in liver cancer cells. HAND2-AS1 augmentation apparently impaired the capacity of liver cancer viability, proliferation, and migration. Cytoplasmic HAND2-AS1 directly bound to miR-3118 and released SOCS5, leading to upregulation of SOCS5. Next, the negative regulator role of SOCS5 in the adjusting JAK-STAT pathway was reconfirmed in this study. Conclusions: HAND2-AS1 enhanced inactivation of the JAK-STAT pathway through sponging miR-3118 and facilitating SOCS5 to retard cell proliferation and migration in liver cancer.