Objective:Our study aimed to identify potential correlations between anti-tumor efficacy and immune-related adverse events (irAEs) in non-small-cell lung cancer (NSCLC).Methods:We conducted a comprehensive search of online electronic databases up to March 2023 to identify any correlations between irAEs and immune checkpoint inhibitor (ICI) efficacy in NSCLC. We used meta-analysis RevMan 5.3 software to calculate pooled results.Results:Our meta-analysis of 54 studies revealed that patients who experienced irAEs achieved a significantly higher objective response rate (p< 0.00001) and longer progression-free survival (PFS) (p< 0.00001) and overall survival (OS) (p< 0.00001) than those who did not experience irAEs. Additionally, patients with ≥2 irAEs had better PFS, whereas no significant difference was observed between patients with or without squamous cell carcinoma. Subgroup analysis of irAE types indicated that irAEs (thyroid dysfunction and gastrointestinal, skin, or endocrine irAEs) were associated with better PFS and OS. However, no significant differences were observed between patients with pneumonitis or hepatobiliary irAEs.Conclusion:Our study showed that the occurrence of irAEs was a strong predictor of survival efficacy in patients with NSCLC treated with ICIs. Specifically, patients with ≥2 irAEs and those with thyroid dysfunction and gastrointestinal, skin, or endocrine irAEs achieved a better survival benefit.Systematic Review Registration:Website:https://www.crd.york.ac.uk/prospero/, Identifier: CRD42023421690