Background: Lung cancer is still one of the most common causes of cancer-related mortality, and the overall survival is less than 5%. It is important and necessary to elucidate the mechanism of lung cancer progression. Recently, more and more research has demonstrated that many ribosomal proteins (RPs) are dysregulated in tumors. Among these RPs, ribosomal protein L6 (RPL6) is reported to promote cell growth and cell cycle progression in gastric cancer cells through upregulating cyclin E. However, its function in lung cancer is still unknown. Methods: We first explored RPL6 expression in lung cancer samples. Next, we used gene knockdown to analyze the unknown regulatory role of RPL6 in lung cancer carcinoma and lung cancer cell lines. Furthermore, we explored the potential signaling pathway of RPL6 with Western blotting. Results: In this study, we demonstrated that RPL6 expression was highly expressed in lung cancer tissues and lung cancer cell lines. RPL6 downregulation inhibited H1299 and H2975 cell proliferation, migration and induced cell apoptosis. Also RPL6 downregulation increased the protein levels of cleaved caspase-3 and Bax, while decreasing the protein level of Bcl-2. Western blotting results showed that proteins activating the AKT signaling pathway, such as p-AKT and p-S6, were downregulated in RPL6 knockdown lung cancer cells. Conclusions: These findings show that RPL6 can be used as a potential therapeutic and preventive biomarker in lung cancer treatment and prognosis by regulating the AKT signaling pathway.