Background Osteoarthritis (OA) is the most common form of human polyarthritis. Many genetic factors have been implicated in OA. It was reported that a polymorphism in the gene of interleukin-6 (IL-6) was associated with OA of knee. The aim of this study was to determine whether functional IL-6 promoter -174G/C (rs1800795) polymorphisms confer susceptibility to knee OA. Methods A meta-analysis was conducted on the association between the IL-6 polymorphism and knee OA. Electronic search at PubMed, EMBASE, Weipu database, and Wanfang database was conducted to select studies. Case-control studies containing available genotype frequencies of IL-6 - 174G/C were chosen, and odds ratio (OR) with 95% confidence interval (CI) was used to assess the strength of this association. Results A total of seven studies involving 6 464 subjects (knee OA 3 331 and controls 3 133) were considered in this study. The results suggested that the variant genotypes were not associated with knee OA risk in all genetic models (additive model: OR=1.144, 95% CI 0.934-1.402, P=0.194; recessive model: OR=1.113, 95% CI 0.799-1.550, P=0.526; dominant model: OR=1.186, 95% CI 0.918-1.531, P=0.191). A symmetric funnel plot, the Begg's test (P >0.05), suggested that the data lacked publication bias. Conclusions This meta-analysis does not support the idea that rs1800795 genotype is associated with increased risk of knee OA. However, to draw comprehensive and more reliable conclusions, further prospective studies with larger numbers of participants worldwide are needed to examine the association between rs1800795 polymorphism and knee OA.