In this study, we found that after upregulating TGFβI and S100A4 expression, ferroptosis in HCC cells was significantly inhibited, and Fe2+ in cells was reduced; silencing the expression of the two promoted the ferroptosis process of HCC and activated the release of Fe2+, confirming that TGFβI and S100A4 have a significant regulatory effect on ferroptosis in HCC. Here, S100A4 is linked to hepatocellular carcinoma.