In summary, we speculated that SLC39A1 inhibited glutathione anabolism and accelerated its decomposition, resulting in impaired the adaption to oxidative stress of RCC cells, and promoted ferroptosis by deregulating the GSH-GPX4 system and altering other key proteins (such as SLC7A11, ACSL4, HO-1, and ferritin), ultimately fostering apoptosis in RCC cells. Here, HMOX1 is linked to renal cell carcinoma.