Lung adenocarcinoma (LAC) represents approximately 40% of all lung cancer cases and is the leading cause of cancer-associated mortality worldwide. Although combined treatment, including radiotherapy, chemotherapy, surgical treatment and immunotherapy, has been used in treating LAC, the five-year survival rate of patients with LAC has not significantly improved. Therefore, it is vital for cancer research to investigate novel prognostic markers and new targets for molecular targeted therapy in LAC. TP53 is an important tumor suppressor gene and is frequently inactivated in lung cancer, thus upregulation or activation of p53 may be a novel targeted therapy for LAC. The present study found that RNF115 mediates ubiquitination of p53 and predicts poor prognosis of patients with LAC. Functionally, it was demonstrated that disruption of RNF115 significantly inhibited cell viability in vitro through inducing G1 phase arrest of LAC cells, which reduced tumor growth in an xenograft model. Taken together, these results suggest that RNF115 could be a novel prognostic biomarker and the RNF115-p53 axis may be a potential target for LAC therapy. (C) 2020 Published by Elsevier Inc.