Patients with advanced liver cancer have poor basic conditions and poor prognosis due to limited treatment options. Sorafenib is the first-line drug approved by FDA for the treatment of advanced liver cancer, and it has multi-kinase inhibitory activity and can improve the survival time of patients with liver cancer. Recent studies have shown that sorafenib is also an inducer of ferroptosis and its toxicity on hepatoma cells partly depends on the induction of ferroptosis of tumor cells. The enhancement of sorafenib-induced ferroptosis can improve the therapeutic effect of sorafenib on liver cancer. At the same time, ferroptosis also plays an important role in the drug-resistance mechanism of sorafenib, and some key proteins involved in the pathways of ferroptosis can also be used to indicate the efficacy of sorafenib and the prognosis of liver cancer. This article reviews the latest research advances in the role of ferroptos in the treatment of liver cancer with sorafenib.