ObjectiveTo evaluate the correlation between interleukin (IL)6 and primary hepatocellular carcinoma (HCC). MethodsCase-control studies that included quantitative data on plasma or serum IL-6 levels of patients with HCC were identified from PubMed, ISI Web of Knowledge, CBM, and CNKI. A meta-analysis was performed to quantitatively and comprehensively analyze data. ResultsTwenty-five studies were included and the meta-analysis was conducted separately for 3 groups: HCC vs controls, HCC vs liver cirrhosis, and HCC vs hepatitis. The serum IL-6 levels of patients with HCC were significantly higher than those of healthy controls (25 studies, standardized mean difference (SMD) 5.02, 95% CI: 4.13-5.91, Z=11.05, P＜0.000 1), patients with liver cirrhosis (15 studies, SMD=236, 95% CI: 1.54-3.19, Z=5.60, P＜0.000 1), and patients with hepatitis (7 studies, SMD=2.63, 95% CI: 1.24-4.03, Z=369, P=0.000 2). ConclusionThe inflammatory mediator, IL-6, may play an important role in the development and progression of HCC.