Notably, the silencing of C12ORF49 enhanced the suppressive effects of Sorafenib on cell growth and induction of ferroptosis in HCC cells, suggesting that C12ORF49 may cause Sorafenib resistance in HCC and its silencing could represent a promising therapeutic strategy to improve the effect of Sorafenib treatment. This evidence concerns the gene SPRING1 and hepatocellular carcinoma.