In the present study, we found that UBL-enriched gene (ABL1, APC, LRP6, FUBP1, KEAP1, and TOP2A) mutation significantly affected atezolizumab efficacy as second-line therapy in NSCLC patients, and we sought to identify a biomarker for potential use in clinical practice in the future. Here, TOP2A is linked to non-small cell lung carcinoma.