Dysregulations in protein kinases significantly contribute to the initiation, progression, and drug resistance in non-small cell lung cancer (NSCLC). Identification of novel oncogenic drivers within the human kinome is crucial for targeted therapy. In this study, we conducted a comprehensive analysis of the TCGA database and literature, pinpointing 16 candidate genes in lung cancer exhibiting frequent dysregulation and limited research. Our functional analysis revealed Serine/threonine kinase 31 (STK31) as a key player in driving tumor growth, in immune-competent mice, with minimal impact in nude mice. Further investigations unveiled upregulation of STK31 led to CD8