Abstract: Objective To discuss the effect of HIF-1α on TGF-β mediated upregulation of ANGPTL4 through down regulating the expression of HIF-1α in A549 cell lines by RNA interference. MethodHIF-1α-shRNA transfected A549 cells(expand discuss the effect of HIF-1 in TGF-β mediated upregulation of ANGPTL4，exprimental group),empty plasmid transfected A549 cells(negative control group) and A549 cells(blank group) were treated with TGF-β1 for various time interval.RT-PCR and Western blot were used to determine the mRNA and protein levels of HIF-1α and ANGPTL4 in the three groups,respectively. Results After TGF-β1 treatment for 0,12,24 or 48h,the mRNA and protein levels of HIF-1α and ANGPTL4 were significantly reduced in comparison with that in negative control and blank groups(P<0.05).Additionally,the mRNA and protein levels of HIF-1α and ANGPTL4 were correlated with action time of TGF-β1 in a time-effect manner in negative control and blank groups (P<0.05).However,the similar changes that regarding to HIF-1 and ANGPTL4 were not observed in experimental groups. Conclusion The probable role of HIF-1 as an upstream regulator of ANGPTL4,may be involved in regulating the TGF-β-Smad pathway mediated overexpression of ANGPTL4.