This study represents the first discovery that PRMT9-mediated arginine methylation of HSPA8 is a key signal regulating ferroptosis in HCC cells, and blocking the methylation modification of HSPA8 by knocking down PRMT9 significantly promoted ferroptosis through CD44 in HCC cells leading to impaired HCC progression (Fig. 8F). This evidence concerns the gene HSPA8 and hepatocellular carcinoma.