Our results indicated that pharmacological inhibition of PTPMT1, facilitated by AD treatment, heightens the susceptibility of HCC to cystine deprivation-ferroptosis, and AD treatment promoted the conversion from ferritin-bound Fe<sup>3+</sup> to free Fe<sup>2+</sup>, which contributed to the labile iron pool in cytoplasm. Here, PTPMT1 is linked to hepatocellular carcinoma.