The application of targeted anticancer drugs has significantly improved the precision and efficacy of cancer treatment. However, the associated hepatotoxicity has become an increasing concern. Tyrosine kinase inhibitors (TKIs), as a crucial class of molecularly targeted drugs, inhibit specific signaling pathways to block tumor cell proliferation and are widely used in the treatment of various malignancies, including lung cancer and leukemia. However, TKIs can induce varying degrees of liver injury through complex mechanisms involving oxidative stress, mitochondrial dysfunction, inflammation, and cholestasis. This study focuses on elucidating the molecular mechanisms of hepatotoxicity induced by crizotinib and sunitinib, while also highlighting the potential of licorice in mitigating TKI-induced liver toxicity. These findings have significant implications for optimizing clinical drug regimens, reducing adverse effects, and ultimately improving patient survival outcomes.