In both HCC tissues and transplanted tumors, we found a robust negative correlation between SOCS2 and SLC7A11 and subsequently confirmed that SOCS2 served as a specific E3 ubiquitin ligase for SLC7A11, promoted ferroptosis by mediating the SLC7A11 degradation, and ultimately led to radiosensitization. Here, SLC7A11 is linked to hepatocellular carcinoma.