Background: Metastasis is one of the principal reasons of cancer mortality from hepatocellular carcinoma (HCC). The goal of our investigation was to examine the mechanism by which arsenic sulfide (As{}_4S{}_4) represses the metastasis of HCC. Methods: The cell counting kit-8 (CCK-8) assay was conducted to observe cell viability of HCC cell lines HepG2 and Hep3B following As{}_4S{}_4 treatment, and their metastasis was studied using the wound-healing and transwell assays. HCC-induced angiogenesis of human umbilical vein endothelial cells (HUVEC) was assessed by tube formation assay. Enzyme-linked immunosorbent assay (ELISA), western blot, quantitative polymerase chain reaction and immunofluorescence staining were utilized to evaluate key molecules involved in metastasis, including hypoxia-inducible factor 1\alpha (HIF-1\alpha), vascular endothelial growth factor (VEGF), Vimentin, N-cadherin and E-cadherin. Results: As{}_4S{}_4 suppressed the proliferation, migration and invasion of HepG2 and Hep3B cell lines in a concentration-dependent pattern, and inhibited HCC cell-induced angiogenesis of HUVEC in the tube formation assay. Treatment with As{}_4S{}_4 also decreased the expression of crucial elements involved in the metastasis of HCC cells, including HIF-1\alpha and VEGF, while reducing epithelial–mesenchymal transition, as shown by Western blot, ELISA and immunofluorescence staining. Conclusions: Overall, results above indicate that As{}_4S{}_4 suppresses the metastasis of HCC cells via the HIF-1\alpha/VEGF pathway.