Considering the data mining of next-generation sequencing (NGS) and whole exome sequencing (WES) in EGFR/anaplastic lymphoma kinase (ALK) non-squamous NSCLC patients treated with ICIs, we used a routine machine learning model based on somatic mutation profiling to develop a genomic signature for predicting the best overall response (BOR) and the prognosis of immunotherapy. The gene discussed is ALK; the disease is non-small cell lung carcinoma.