Background: The significance of interleukin-10(IL-10) on the susceptibility of malignant tumor is one of the hot spots of current research. 1082A > G (rs1800896) and -819C > T (rs1800871) are two genetic variants of IL-10, and their effects on malignancy need to be further explored. Therefore, in order to further explore the relationship between IL-10 polymorphisms and cancer susceptibility and the role of IL-10 in the occurrence and development of malignant tumors, in this paper, we use of odds ratios (ORs), corresponding 95% confidence intervals (CIs), and in silico tools. analysis to study the relationship between the two. Furthermore, GSEA was used to analyze the expression of IL-10 in renal cell carcinoma, bladder cancer and prostate cancer. We conducted a systematic analysis of 50 controlled trials involving 15,418 cancer patients and 18,597 controls. The analysis showed that the -1082A>G (rs1800896) and -819C>T (rs1800871) polymorphism were associated with the risk of bladder cancer. GSEA showed that IL-10 was highly expressed through the Cytokine-Cytokine-receptor-interaction pathway, JSK-STAT-signaling pathway, Natural killer cell mediated cytotoxicity pathway and Leukocyte transendothelial migration pathway.