Objective To investigate the role and mechanism of fatty acid binding protein 5 (FABP5) in hypoxia induced angiogenesis in hepatocellular carcinoma. Methods Huh7 cells were cultured under normal and anaerobic conditions; FABP5 siRNA was transfected to knock down the expression of FABP5 in Huh7 cells; the expression of FABP5 mRNA was detected by reverse transcription PCR; the expressions of FABP5 and vascular endothelial growth factor A (VEGFA) were detected by Western blot; the concentration of VEGFA in the supernatant of Huh7 cells was detected by ELISA; and the angiogenesis of human umbilical vein endothelial cells (HUVECs) induced by the supernatant of Huh7 cells was detected by tube formation assay. Results After anaerobic culture, the expressions of FABP5 mRNA and FABP5 and VEGFA proteins were increased; after FABP5 siRNA transfection, the expression and secretion of VEGFA in anaerobic cultured Huh7 cells were decreased and the angiogenesis of HUVECs induced by supernatant of anaerobic cultured Huh7 cells were decreased. Conclusion Hypoxia induces an increase in the expression of FABP5 in Huh7 cells, and knocking down FABP5 inhibits the expression of VEGFA in Huh7 cells and the angiogenesis of HUVEC.