Lung cancer is one of the most common malignant tumors and is currently the leading cause of cancer-related deaths worldwide. Although the treatment strategy has been significantly improved, the prognosis of lung cancer patients is still quite poor. RIOK1 has been reported to be highly expressed in non-small cell lung cancer (NSCLC), however, its clinical significance and biological function are still largely unknown in lung cancer. Using western blot and immunohistochemistry, we showed that RIOK1 was highly expressed in NSCLC tissues and correlated with advanced stage and poor prognosis. Furthermore, knockdown of RIOK1 could inhibit proliferation, migration, and invasion in NSCLC cells and tumorigenesis