The results revealed that knockdown of TFRC rescued the cell phenotype caused by USP22 knockout, leading to the inhibition of Sorafenib‐induced ferroptosis, as evidenced by increased cell viability (Figure 7B), decreased percentages of cell death (Figure 7C), decreased cellular lipid ROS level (Figure 7D), promoted GSH level (Figure 7E) and reduced Fe2+ level (Figure 7F) in USP22‐depleted hepatocellular carcinoma cells upon Sorafenib treatment. Here, TFRC is linked to hepatocellular carcinoma.