Objective To investigate the effect of LASP-1 expression silencing by specific small interfering RNA (siRNA) on HepG2 cell proliferation and migration. Methods small interfering RNA (siRNA) targeting LASP-1 were designed and transfected into HepG2 cells by lipofectamine. Western blotting was used to evaluate the effect of siRNA. When the expression level of LASP-1 was downregulated after successful transfection, cell proliferation was detected by CCK-8 assay and the plate colony formation assay. The migration ability of cells was detected by transwell assay and wound healing assay. Results (1) Western blotting results revealed that LASP-1 siRNA notably downregulated the expression of LASP-1 protein (P<0. 05). (2) Downregulation of LASP-1 expression distinctly inhibited the proliferation of the HepG2 cells (P < 0.05 ). The migration ability of HepG2 cells in vitro was decreased significantly after siRNA targeting LASP-1 was successful transfected (P<0.05). Conclusion LASP-1 might play an important role in HepG2 cell proliferation and migraion, indicating that LASP-1 may be a novel and effective therapeutic target for preventing hepatocellular carcinoma proliferation and migration.