The MR analysis of the causal relationship between the 14 key genes and mesothelioma revealed that the expression levels of MPZL1 (OR = 1.728; 95% CI: [1.143–2.612]; P = 0.009), SOAT1 (OR = 1.579; 95% CI: [1.050–2.374]; P = 0.028), TACC3 (OR = 1.964; 95% CI: [1.057–3.649]; P = 0.033), and CYBRD1 (OR = 1.771; 95% CI: [1.019–3.078]; P = 0.043) were positively correlated with mesothelioma. The gene discussed is CYBRD1; the disease is mesothelioma.