These results implied that CISD1 was an important target of GCN5L1 to regulate the sensitivity of HCC to sorafenib, and CISD1 inhibitor in combination with sorafenib could enhance the therapeutic effect in sorafenib sensitive HCC and re-sensitize sorafenib resistant cells, which would be a potentially pharmaceutical strategy for clinical therapy. This evidence concerns the gene CISD1 and hepatocellular carcinoma.