Recent studies suggest that high expression of the pro-inflammatory cytokine interleukin-6 (IL-6) is associated with poor survival of lung cancer patients. Accordingly, IL-6 has been a target of great interest for lung cancer therapy. However, the role of IL-6 in lung cancer has not been determined yet. Here, we demonstrate that IL-6 plays opposite roles in the initiation and growth of lung cancer in a mouse model of lung cancer induced by the K-Ras oncogene. We find that compared to wild type mice, IL-6 deficient mice developed much more lung tumors after an activating mutant of K-Ras was induced in the lungs. However, lung tumors developed in IL-6 deficient mice were significantly smaller. Notably, both the lung tumor-suppressing and -promoting functions of IL-6 involve its ability in activating the transcription factor STAT3. IL-6/STAT3 signaling suppressed lung cancer initiation through maintaining lung homeostasis, regulating lung macrophages and activating cytotoxic CD8 T cells under K-Ras oncogenic stress, whereas it promoted lung cancer cell growth through inducing the cell proliferation regulator Cyclin D1. These studies reveal a previously unexplored role of IL-6/STAT3 signaling in maintaining lung homeostasis and suppressing lung cancer induction. These studies also significantly improve our understanding of lung cancer and provide a molecular basis for designing IL-6/STAT3-targeted therapies for this deadliest human cancer.