Transforming growth factor-β (TGF-β) plays a dual role in cancer, initially suppressing tumorigenesis by inhibiting cell cycle progression and inducing apoptosis, but later promoting cancer progression through mechanisms such as angiogenesis, immune suppression, and epithelial-to-mesenchymal transition (EMT). TGF-β expression is associated with poor prognosis in various cancers, including poor tissue differentiation, advanced stages, and metastasis. However, TGF-β inhibition can enhance anti-tumor effects, especially when combined with radiotherapy. TGF-β signaling pathways include canonical Smad and non-canonical pathways, with the canonical pathway involved in cell cycle arrest and apoptosis, while non-canonical pathways contribute to tumor growth. TGF-β receptor mutations and downstream signaling disruptions can lead to resistance to therapy. TGF-β also promotes tumor invasion and metastasis by enhancing angiogenesis, immune evasion, and ECM degradation. TGF-β inhibitors are being tested in clinical trials, showing potential for anti-tumor therapy. Despite these findings, challenges remain in targeting TGF-β without affecting host functions. TGF-β levels are linked to treatment resistance and poor prognosis, suggesting its role as a potential therapeutic target. Further research is needed to optimize TGF-β targeting strategies for cancer treatment.Transforming growth factor-β (TGF-β) plays a dual role in cancer, initially suppressing tumorigenesis by inhibiting cell cycle progression and inducing apoptosis, but later promoting cancer progression through mechanisms such as angiogenesis, immune suppression, and epithelial-to-mesenchymal transition (EMT). TGF-β expression is associated with poor prognosis in various cancers, including poor tissue differentiation, advanced stages, and metastasis. However, TGF-β inhibition can enhance anti-tumor effects, especially when combined with radiotherapy. TGF-β signaling pathways include canonical Smad and non-canonical pathways, with the canonical pathway involved in cell cycle arrest and apoptosis, while non-canonical pathways contribute to tumor growth. TGF-β receptor mutations and downstream signaling disruptions can lead to resistance to therapy. TGF-β also promotes tumor invasion and metastasis by enhancing angiogenesis, immune evasion, and ECM degradation. TGF-β inhibitors are being tested in clinical trials, showing potential for anti-tumor therapy. Despite these findings, challenges remain in targeting TGF-β without affecting host functions. TGF-β levels are linked to treatment resistance and poor prognosis, suggesting its role as a potential therapeutic target. Further research is needed to optimize TGF-β targeting strategies for cancer treatment.