Although serum albumin and neuroticism have been found to be strongly associated with suicidal ideation in depressed patients, the causal relationship is uncertain. In the present study, the separate causal association of serum albumin with neuroticism and suicidal ideation was analyzed using univariable Mendelian Randomization (UVMR) methods via large-scale GWAS data. The multivariable MR (MVMR) analysis was used to explore causal pathways. UVMR results showed that genetically determined serum albumin was causally associated with neuroticism (β=0.009 S.D.; 95% CI: 0.001, 0.016; p=0.037) and suicidal ideation (β=0.120 S.D.; 95% CI: 0.059, 0.0180; p<0.001). MVMR results showed that neuroticism mediated 100% of the causal association between serum albumin and suicidal ideation in depressed patients. These findings suggest strong genetic evidence for the causal effect of serum albumin on suicidal ideation in depressed patients, and the complete mediation effect of neuroticism on this causal association. This study provided an evidence that serum albumin and personality traits are potential risks of suicidal ideation in patients with depression and a better approach for the intervention of suicidal ideation in depressed patients.