BACKGROUND: Asthma is the most common chronic disease among children and poses a major threat to their health. Observational studies have shown lipid disorders in children with asthma. However, it was not possible to determine whether there is a causal link between the two. Therefore, the aim of this study was to assess the causal relationship between serum liposomes and asthma in children. METHODS: We used large-scale publicly available genome-wide association study summary statistics to elucidate causal associations between plasma liposomes and children using a two-sample Mendelian randomization (MR) approach. The IVW method was used as the primary analysis method, and tests such as the Cochran Q test, MR-Egger intercept, and leave-one-out method were utilized to explore whether there was heterogeneity and pleiotropy in the MR results. In addition, Steiger's test and reverse MR analysis were performed to test the directionality of the MR results. RESULTS: Our MR results identified a causal link between six plasma liposomes and childhood asthma. Among them, negative association between Diacylglycerol (16:0_18:2) (OR = 0.952, 95%CI = 0.913-0.992, p = 0.018), Triacylglycerol (52:4) (OR = 0.949, 95%CI = 0.905-0.994, p = 0.028), Phosphatidylcholine (18:2_20:3) (OR = 0.915, 95%CI = 0.843-0.993, p = 0.034), sterol ester (27:1/22:6) (OR = 0.929, 95% CI = 0.869-0.994, p = 0.031) and childhood asthma. There is a positive association between Phosphatidylcholine (16:0_22:5) (OR = 1.061, 95%CI = 1.006-1.120, p = 0.030), sterol ester (27:1/20:4) (OR = 1.046, 95% CI = 1.021-1.072, p = 0.0003) and pediatric asthma. A series of sensitivity tests also demonstrate the robustness of the results. CONCLUSION: This MR study identified a causal link between some plasma liposomes and childhood asthma. This will provide new perspectives on the prevention and treatment of childhood asthma in the future.