This study meta-analyzed the literature on possible association of polymorphisms -137 (rs187238) and -607 (rs1946518) in the interleukin-18 (IL-18) promoter with risk of hepatocellular carcinoma (HCC). The analysis included 8 case-control studies on the -137 polymorphism (1,318 cases, 2,254 controls) and 7 case-control studies on the -607 polymorphism (1,262 cases, 1,696 controls). None of the five genetic models suggested a significant association between the -137 polymorphism and HCC risk: allelic model, OR 0.99, 95% CI 0.74-1.34, P = 0.97; recessive model, OR 0.98, 95% CI 0.65-1.46, P = 0.91; dominant model, OR 1.35, 95% CI 0.73-2.52, P = 0.34; homozygous model, OR 0.99, 95% CI 0.65-1.49, P = 0.95; heterozygous model, OR 0.99, 95% CI 0.66-1.48, P = 0.94. Similar results were obtained in subgroup analyses of Asian patients, Chinese patients, or patients with hepatitis B virus (HBV)-related HCC. Similar results were also obtained for the -607 polymorphism across the entire study population as well as in the three subgroups. The available evidence suggests no significant association of the -137 or -607 polymorphisms with risk of HCC in general or specifically of HBV-related HCC. These conclusions should be verified in large, well-designed studies.