BACKGROUND: Neuroticism, a personality trait characterized by emotional instability, has been linked to an increased risk of lung cancer (LC). However, the genetic underpinnings of this association remain poorly understood. This study aimed to comprehensively dissect the genetic link underlying neuroticism and LC. METHODS: We used genome-wide association study (GWAS) data to investigate the intricate genetic relationship between neuroticism and LC, along with specific histological subtypes: lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC), and small-cell LC (SCLC). Our analytical framework encompassed global and local genetic correlation, cross-trait meta-analysis, transcriptome-wide association study (TWAS), and bidirectional Mendelian randomization (MR) analysis. RESULTS: Notable genetic correlations were found between neuroticism and overall LC (r CONCLUSIONS: This study reveals a genetic link between neuroticism and LC, offering new insights into LC risk assessment and potential prevention strategies for individuals with high neuroticism levels.