Background: Hepatocellular carcinoma is an aggressive disease in Asia and Africa with poor prognosis partially due to lack of disease-specific biomarkers. Objectives: The aim of this study was to assess the concentrations of different cytokines and chemokines in peripheral blood of patients with hepatocellular carcinoma and identify the potential biomarkers that would help in clinical assessment. Methods: Profiling of 14 cytokines, chemokines and growth factors was performed in peripheral blood of 78 patients and 78 healthy controls using Bio-Plex Human 15-plex assay kit. Results: The results showed that patients had significantly higher levels of IL-1β (p=0.034), IL-6 (p=2.13e-06),IL-10 (p=0.013), IL-17A (p=0.017), IL-22 (p=0.00276), IL-25 (p=0.0005), but lower levels of IL-4 (p=0.00341) and IL-33 (p=0.00982) in peripheral blood. Conclusion: We identified a unique eight-peripheral blood cytokines signature for hepatocellular carcinoma detection. This work will serve as the basis for further studies about the clinical value of peripheral blood cytokines in forecasting prognosis