Kirsten rat sarcoma viral oncogene homolog (KRAS) oncogenic mutations are genetic drivers in various cancers, including non-small cell lung cancer (NSCLC). However, the regulatory mechanisms underlying the progression of NSCLC driven by oncogenic KRAS mutants are incompletely understood. Here, we show that ubiquitin specific peptidase 25 (USP25) impedes ring finger protein 31 (RNF31)-mediated linear ubiquitination of KRAS oncogenic mutants (KRAS