Objective:To investigate the effect of hepatocyte nuclear factor 4α (HNF4α) on the angiogenesis related genes of CBRH-7919 in vitro and in vivo. Methods: CBRH-7919 cells were transfected with HNF4α adenovirus vector. CBRH-7919 cell proliferation was detected by cell counting kit-8 (CCK8) assay and the migration and invasion were assessed by Transwell assays. The expressions of Angiopoietin-2 (Ang-2) and vascular endothelial growth factor (VEGF) were detected by RT-PCR and Western blotting assay. In vivo, CBRH-7919 cells, CBRH-7919-Null-Vector cells and CBRH-7919-HNF4α cells were respectively injected into the rest of the liver after establishment of subtotal hepatectomy model (70%). Four weeks later, the expressions of Ang-2 and VEGF in the liver tissues were detected by immunohistochemical assay. Results: In vitro study indicated that after transfected with adenovirus vector LV-HNF4α,the proliferation of CBRH-7919 was significantly inhibited (P < 0.05) and the invasiveness was also significantly inhibited (P < 0.05)compared with the control group,respectively. The result of RT-PCR suggested that the expressions of Ang-2 and VEGF were inhibited after transfected with adenovirus vector. In vivo study showed similar finding that the expressions of Ang-2 and VEGF were inhibited after transfected with adenovirus vector(P < 0.05). Conclusion: HNF4α can significantly inhibit proliferation and metastasis capability of CBRH-7919, as well as inhibits the expression of Ang-2 and VEGF in CBRH-7919.