Chronic inflammation and cytokines in the tumor microenvironment play a critical role in cancer development. Inflammation, initially a beneficial response to tissue damage, can become chronic and promote malignant transformation. Cytokines such as TNF-α, IL-6, TGF-β, and IL-10 are involved in both the initiation and progression of cancer. These cytokines contribute to carcinogenesis through mechanisms like reactive oxygen and nitrogen species (RONS) generation, DNA damage, epithelial-mesenchymal transition (EMT), angiogenesis, and metastasis. Chronic inflammatory diseases, such as inflammatory bowel disease (IBD) and primary sclerosing cholangitis (PSC), are linked to cancers like colorectal cancer and cholangiocarcinoma (CCA). TNF-α promotes tumor growth and progression, while IL-6 and TGF-β have dual roles in cancer, acting as both promoters and suppressors. IL-10, an anti-inflammatory cytokine, can have both pro- and anti-tumoral effects. Inflammation-induced RONS contribute to DNA damage and carcinogenesis. Inflammatory cytokines also influence angiogenesis, which is essential for tumor growth and metastasis. The interplay between these cytokines and the tumor microenvironment is complex, with factors like EMT, immune evasion, and tumor cell proliferation playing key roles. In colorectal cancer, chronic inflammation from IBD increases cancer risk, with factors like prolonged disease duration and concomitant PSC contributing to higher risk. In CCA, PSC and liver fluke infections are major risk factors. Cytokines such as TNF-α, IL-6, and IL-17 are involved in the progression of these cancers. Understanding the role of cytokines in inflammation and cancer is crucial for developing targeted therapies. The review highlights the importance of managing chronic inflammation to reduce cancer risk and the potential of cytokine-targeting therapies in cancer treatment.Chronic inflammation and cytokines in the tumor microenvironment play a critical role in cancer development. Inflammation, initially a beneficial response to tissue damage, can become chronic and promote malignant transformation. Cytokines such as TNF-α, IL-6, TGF-β, and IL-10 are involved in both the initiation and progression of cancer. These cytokines contribute to carcinogenesis through mechanisms like reactive oxygen and nitrogen species (RONS) generation, DNA damage, epithelial-mesenchymal transition (EMT), angiogenesis, and metastasis. Chronic inflammatory diseases, such as inflammatory bowel disease (IBD) and primary sclerosing cholangitis (PSC), are linked to cancers like colorectal cancer and cholangiocarcinoma (CCA). TNF-α promotes tumor growth and progression, while IL-6 and TGF-β have dual roles in cancer, acting as both promoters and suppressors. IL-10, an anti-inflammatory cytokine, can have both pro- and anti-tumoral effects. Inflammation-induced RONS contribute to DNA damage and carcinogenesis. Inflammatory cytokines also influence angiogenesis, which is essential for tumor growth and metastasis. The interplay between these cytokines and the tumor microenvironment is complex, with factors like EMT, immune evasion, and tumor cell proliferation playing key roles. In colorectal cancer, chronic inflammation from IBD increases cancer risk, with factors like prolonged disease duration and concomitant PSC contributing to higher risk. In CCA, PSC and liver fluke infections are major risk factors. Cytokines such as TNF-α, IL-6, and IL-17 are involved in the progression of these cancers. Understanding the role of cytokines in inflammation and cancer is crucial for developing targeted therapies. The review highlights the importance of managing chronic inflammation to reduce cancer risk and the potential of cytokine-targeting therapies in cancer treatment.