In the current study, sorafenib could inhibit the colony and migration of HCC cells, but overexpression of IF1 could attenuated the effect of sorafenib in Hep3B or Huh7 cells, and inhibition of IF1 could improve sorafenib effect in Hep3B-H or Huh7-H cells. This evidence concerns the gene ATP5IF1 and hepatocellular carcinoma.