Aim: Alpha-fetoprotein (AFP) is still the most commonly used and the single most recommended marker in the diagnosis of hepatocellular carcinoma (HCC). Interleukin (IL)-6 is a circular cytokine and its role on carcinogenesis in various hematological and solid tumors is clearly documented. A combination of serum IL-6 and AFP may provide beneficial information regarding early diagnosis of HCC. In this study, the effect of plasma IL-6 level in the diagnosis of HCC was investigated. Materials and methods: A total of 130 patients with liver cirrhosis, together with 30 control cases were enrolled in the trial. A diagnosis of HCC was present in 75 patients (57.6%) in the liver cirrhosis group. Blood samples were obtained from the enrolled study and control cases. Alpha-fetoprotein was quantified by chemiluminescent method. Plasma IL-6 levels of samples obtained at –80°C were quantified by human IL-6 BMS213/2 BMS213/2TEN kit. Results: The HCC patients were older than the patients in the cirrhosis group (p = 0.016). On comparison of the HCC patients with the control group, AFP (p < 0.001) and IL-6 (p < 0.001) were significantly higher among the HCC patients. Comparison of HCC patients with liver cirrhosis cases with no diagnosis of HCC revealed significantly high AFP (p < 0.001) and IL-6 levels (p < 0.001) in HCC group. Cutoff value for IL-6 was calculated as 5.73 (pg/mL). No difference was detected in AFP (p = 0.600) and IL-6 (0.344) in all three subgroups. A total of 17 patients died during a mean follow-up period of 32.9 months. No correlation was found between mean AFP values and IL-6 values and survival rates. Conclusion: Plasma IL-6 level was found to be significant in the diagnosis of HCC. Alpha-fetoprotein and IL-6 provided no advantage in terms of early diagnosis of HCC and no correlation was observed between these markers and survival.