Lung adenocarcinoma (LUAD) remains a major reason of cancer-associated mortality globally, and there exists a lack of indicators for survival in LUAD patients. Therefore, it is clinically required to obtain a novel prognostically indicator for guiding clinical management. In this study, we established a circadian rhythm (CR) related signature by a combinative investigation of multiple datasets. The newly-established signature showed an acceptable ability to predict survival and could serve as an independent indicator for prognosis. Moreover, the newly-established signature was critically associated with tumor malignancy, including proliferation, invasion, EMT and metastasis. The newly-established signature was predictive of response to immune checkpoint blockade. Collectively, we established a CR-related gene signature that could forecast survival, tumor malignancy and therapeutic response; our findings could help guiding clinical management.