Abstract: Objective: To explore the effect of LRRFIP1 upregulation on the biological behavior of hepatocellu-lar carcinoma cell Huh7, and to preliminarily explore its related mechanism.Methods: Stable cell line with LR-RFIP1 overexpression was constructed, and the overexpression efficiency was detected by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR)and western blotting.The effect of LRRFIP1 overexpression on the proliferation ability of Huh7 cells was detected by CCK-8; the effect of overexpression of LRRFIP1 on the clonogenic ability of Huh7 cells was detected by plate cloning experiment; the effect of overexpression of LR-RFIP1 on cell cycle and apoptosis was detected by flow cytometry; the effect of overexpression of LRRFIP1 on the migration and invasion of Huh7 cells was detect-ed by scratch assay and Transwell assay; western blot-ting was performed to detect the expressions of pro-teins E-cadherin, N-cadherin, Ⅴimentin and Snail re-lated to epithelial- mesenchymal transition (EMT).CoIP-MS was used to screen the proteins that might interact with LRRFIP1.Results: Overexpression of LR-RFIP1 promoted the proliferation (P< 0.001) and clonogenic ability (P< 0.001) of Huh7 cells and inhibited cell apoptosis(P< 0.01); overexpression of LRRFIP1 resulted in an decrease proportion in G0/G1 phase and S phase of Huh7 cells (P< 0.001, P< 0.01).In addition, the number of cell migration (P< 0.05) and invasion (P< 0.001)in the LRRFIP1 overexpression group was significantly lower than that in the control group.Western blotting re-sults showed that compared with the control group, the expression of epithelial marker protein E-cadherin in the overexpressed LRRFIP1 group significantly increased (P< 0.001), the expressions of mesenchymal marker pro-teins N-cadherin, Ⅴimentin and the expression of EMT-related transcription factor Snail protein significantly de-creased (P< 0.001, P< 0.01, P< 0.001).Finally, after overexpression of LRRFIP1, CoIP-MS was used to screen 80 proteins that might interact with LRRFIP1.GO analysis showed that the LRRFIP binding proteins in Huh7 cell line was enriched in 27 biological processes, 11 cell components and 9 molecular functions.KEGG pathway annotation showed that these 80 proteins were mainly enriched in ECM-receptor interaction signal pathway; STRING and Cytoscape analyzed the Hub genes.Conclusion: LRRFIP1 overexpression can promote the prolifer-ation and the clonogenic ability of Huh7 cells, inhibit their apoptosis, migration and invasion, and may interact with eEF1A1, thus affecting the occurrence and development of Hepatocellular carcinoma.