Background: Colorectal cancer is the fourth most common cause of cancer mortality worldwide. Pathophysiology implicates pro-inflammatory conditions that promote tumor progression. The aim of this study is to measure level of cytokines: interleukin (IL) 1β, IL6, IL8, IL10, IL22, IL23 and TNFα and evaluate their prognostic implication. Methods: Serum samples were collected prospectively from a cohort of sixty colorectal cancer patients in Tunisia. Levels of TNF-α, IL1β, IL6 and IL8 were measured using the technique of a solid-phase, two-site chemo-luminescent enzyme immune-metric assay. Serum levels of IL10 were measured by enzyme-linked immunosorbent assays (ELISA) sandwich method. Results: The mean age of patients is 58 years (24–82 years), with sex ratio of 1.5. Twenty-five patients were metastatic, with hepatic metastasis in 25% of cases. The mean level of IL6, IL10, TNFα, IL8 and IL1β were respectively 12.29 +/- 18.7pg/ ml, 0.93 +/- 5.23 pg/ ml, 8.31 +/- 4.99 pg/ ml, 61.9 +/- 159.71pg/ml and 1.13 +/- 3.34 pg/ ml. We found a significant correlation between a high level of IL8 and metastatic disease (p=0.000), especially in mutant RAS cases (p=0.001). We found also a significant correlation between high level of IL1β and lymphovascular invasion (p=0.013) and young patients (p=0.01). On the other hand, there was significant correlation between IL8 and IL6 (p=0.00001); IL8 and TNFα (p=0.001); and IL10 with IL1β(p=0.021). Conclusions: Our results highlight the role of circulating IL8, TNFα, IL1β and IL10 as potential prognostic biomarkers in colorectal cancer patients, namely for IL-8.