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Colorectal cancer (CRC) remains one of the most important global health problems, being in the top 3 neoplasms in terms of the number of cases worldwide. Although CRC develops predominantly from the adenoma–adenocarcinoma sequence through APC gene mutations, in recent years, studies have demonstrated the role of chronic inflammation in this neoplasia pathogenesis. Cytokines are important components of chronic inflammation, being some of the host regulators in response to inflammation. The pro-inflammatory cytokines IL-1β, IL-6, and TNF-α are involved in tumor cell proliferation, angiogenesis, and metastasis and seem to strengthen each other's mode of action, these being stimulated by the same mediators. In our study, we collected data on 68 patients with CRC and 20 healthy patients from the Gastroenterology Department of Craiova County Emergency Clinical Hospital, who were assessed between January 2022 and February 2023. The main purpose of this study was to investigate the correlation between increased plasma levels of the cytokines and the extent of the tumor, lymph nodes, and metastasis—(TNM stage), as well as the patients' prognoses. We also compared the plasma levels of cytokines and acute inflammatory markers, namely, the erythrocyte sedimentation rate (ESR), c-reactive protein (CRP), and fibrinogen, along with the tumor markers, carcinoembryonic antigen (CEA) and carbohydrate antigen 19.9 (CA 19.9), in CRC patients. We showed that all the pro-inflammatory cytokines studied had higher levels in patients with CRC in comparison with the control group. We also showed that the acute inflammatory markers of erythrocyte sedimentation rate, C-reactive protein, and fibrinogen, and the tumor markers of CEA and CA 19.9 can be useful in diagnosis and prognosis in patients with CRC. Considering the association between pro-inflammatory cytokines and CRC, the development of new targeted therapies against IL-1β, IL-6, and TNF-α can improve patient care and the CRC survival rate. [ABSTRACT FROM AUTHOR]