Abstract: Objective Two-sample Mendelian randomization (MR) analysis was used to investigate the relationship between different interleukins and gynecological tumors, including cervical cancer, endometrial cancer and uterine leiomyoma. Methods Using the IEU OpenGWAS open database, interleukin and gynecological tumor data were obtained from European populations. Two-sample MR Analysis was applied, different interleukins were used as exposure factors, significant SNPS in GWAS data were selected as instrumental variables, and the instrumental variables were independent of each other. The risk of three kinds of gynecological tumors was analyzed separately to explore the causal relationship between interleukin predicted by genes and outcome indicators. The TwoSampleMR package in R language (4.3.1) software was used for statistical analysis. Perform MR analysis using inverse variance weighted (IVW), MR Egger regression, weighted median (WM), simple mode (SM), and weighted mode (WM) methods. The analysis results are presented as Odds Ratio (OR) and 95% CI. To evaluate whether there is potential bias in the results of MR analysis, and whether there is a significant impact of an instrumental variable on the outcome variable, sensitivity analysis should be conducted using methods including heterogeneity testing, horizontal pleiotropy analysis, and retention method sensitivity testing. Results Genetic prediction of IL-18 receptor 1 (IVW: OR=0.999, 95% CI: 0.998-1.000, p=3.90E-02) and IL-24 (IVW: OR=0.999, 95% CI: 0.998-1.000, p=2.46E-02) were negatively correlated with the risk of cervical cancer; IL-4 (IVW: OR=1.091, 95% CI: 1.004-1.186, p=3.98E-02), IL-21 (IVW: OR=1.069, 95% CI: 1.008-1.133, p=2.59E-02) and IL-37 (Weighted median: OR=1.112, 95% CI: 1.012-1.221, p=2.66E-02) were positively correlated with the risk of endometrial cancer; IL-15 receptor subunit alpha (IVW: OR=0.932, 95% CI: 0.887-0.978, p=4.63E-03) was negatively correlated with the risk of endometrial cancer; IL-17A (IVW: OR=0.998, 95% CI: 0.997-0.999, p=5.20E-03) and IL-37 (Weighted median: OR=0.999, 95% CI: 0.998-1.000, p=1.75E-02) were negatively correlated with the risk of uterine leiomyoma; IL-21 (IVW: OR=1.001, 95% CI: 1.000-1.002, p=3.51E-02) was positively correlated with the risk of uterine leiomyoma. The results of the MR-Egger-intercept analysis did not detect potential horizontal pleiotropic effects, indicating that the instrumental variables did not significantly affect the outcomes of the three gynecological tumors through pathways other than interleukin. Cochran's Q heterogeneity test suggested potential heterogeneity in the MR analysis results of IL-4 and endometrial cancer (MR Egger: p=0.04), but there was no significant heterogeneity between other interleukins and gynecological tumors. The sensitivity test results of the retention method show that the MR analysis results generated by sequentially removing individual SNPs are basically consistent with the MR analysis results of including all SNPs, with an estimated error line of about 0, indicating that there is no impact of a single SNP on the overall causal estimation. The funnel plot results show that the distribution of included SNPs is basically balanced and not affected by potential factors, resulting in bias. Conclusion Genetically predicted IL-4, IL-15Rα, IL-17A, IL-18R1, IL-21, IL-24, and IL-37 were causally associated with the risk of three gynecological tumors. Further exploration of the molecular mechanism of interleukin in gynecological tumors may provide potential therapeutic targets for the treatment of gynecological tumors.