Cytokines are important modulators in the interactions between the host immune system and malignant tumor. Of these, Interleukin-10 (IL-10) is an important immunoregulatory cytokine mainly produced by macrophages and T lymphocytes. To date, a number of studies investigated the role of the IL-10-819C>T polymorphism in the aetiology of cancers of various organs. However, the results of these studies remain inconclusive. So, we carried out a meta-analysis on all eligible case-control studies to estimate the overall cancer risk of IL-10-819C>T polymorphism as well as to quantify the between-study heterogeneity and potential bias. This meta-analysis, including 8157 cases and 10 473 controls from 29 published case–control studies, explored the association between a potentially functional polymorphism, -819C>T within the IL-10 promoter region and cancer risk. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. The results provided evidence that the IL-10-819C>T polymorphism was associated with a significant decrease in overall cancer risk. In the stratified analyses, the risk remained for studies of “other cancer”, smoking-related cancer, Asian populations and hospital-based studies. This meta-analysis identified an evidence of the association between the IL-10-819C>T and cancer risk, especially in “other cancer”, smoking-related cancers, Asians and hospital-based studies. Further large case–control studies, especially studies in African population were needed to validate our results.