Liver cancer remains a major global health issue with high incidence and mortality rates. Due to its subtle onset, liver cancer is often diagnosed at an advanced stage, limiting surgical options. Targeted therapies, particularly tyrosine kinase inhibitors (TKIs) like sorafenib, are crucial for improving patient outcomes. However, drug resistance remains a significant challenge. This review explores the signaling pathways involved in liver cancer pathogenesis and the inhibitors targeting these pathways. It emphasizes the oncogenic roles of these pathways, especially in hepatocellular carcinoma (HCC), and the current state of research on inhibitors. Given the limited effectiveness of TKIs, there is an urgent need for innovative targeted strategies to overcome resistance and improve treatment outcomes. Liver cancer pathogenesis involves multiple signaling pathways, including those related to growth factor receptors, Wnt-β-catenin, JAK/STAT, Hedgehog, Hippo, Notch, and NF-κB. These pathways regulate cell proliferation, survival, and tumor progression. The VEGF pathway is particularly significant in angiogenesis and tumor growth. FGFR4 and FGF signaling are also implicated in HCC progression. TGF-β signaling has dual roles in tumor suppression and promotion, with dysregulation contributing to HCC development. EGFR and IGF signaling are also critical in liver cancer progression. The c-Met pathway is involved in liver regeneration and tumor growth. PDGF signaling promotes liver fibrosis and cancer development. The Ras/Raf/MEK/ERK and PI3K/AKT/mTOR pathways are key regulators of cell growth and survival. Dysregulation of these pathways is associated with HCC progression. The Wnt-β-catenin pathway is involved in liver cell differentiation and tumor development. The JAK/STAT pathway is linked to HCC progression through inflammatory and oxidative stress mechanisms. Understanding these pathways and their interactions is essential for developing effective targeted therapies. Current research focuses on inhibitors targeting these pathways, with a particular emphasis on overcoming resistance mechanisms. This review highlights the importance of targeting these pathways to improve the prognosis of liver cancer patients.Liver cancer remains a major global health issue with high incidence and mortality rates. Due to its subtle onset, liver cancer is often diagnosed at an advanced stage, limiting surgical options. Targeted therapies, particularly tyrosine kinase inhibitors (TKIs) like sorafenib, are crucial for improving patient outcomes. However, drug resistance remains a significant challenge. This review explores the signaling pathways involved in liver cancer pathogenesis and the inhibitors targeting these pathways. It emphasizes the oncogenic roles of these pathways, especially in hepatocellular carcinoma (HCC), and the current state of research on inhibitors. Given the limited effectiveness of TKIs, there is an urgent need for innovative targeted strategies to overcome resistance and improve treatment outcomes. Liver cancer pathogenesis involves multiple signaling pathways, including those related to growth factor receptors, Wnt-β-catenin, JAK/STAT, Hedgehog, Hippo, Notch, and NF-κB. These pathways regulate cell proliferation, survival, and tumor progression. The VEGF pathway is particularly significant in angiogenesis and tumor growth. FGFR4 and FGF signaling are also implicated in HCC progression. TGF-β signaling has dual roles in tumor suppression and promotion, with dysregulation contributing to HCC development. EGFR and IGF signaling are also critical in liver cancer progression. The c-Met pathway is involved in liver regeneration and tumor growth. PDGF signaling promotes liver fibrosis and cancer development. The Ras/Raf/MEK/ERK and PI3K/AKT/mTOR pathways are key regulators of cell growth and survival. Dysregulation of these pathways is associated with HCC progression. The Wnt-β-catenin pathway is involved in liver cell differentiation and tumor development. The JAK/STAT pathway is linked to HCC progression through inflammatory and oxidative stress mechanisms. Understanding these pathways and their interactions is essential for developing effective targeted therapies. Current research focuses on inhibitors targeting these pathways, with a particular emphasis on overcoming resistance mechanisms. This review highlights the importance of targeting these pathways to improve the prognosis of liver cancer patients.