Lung cancer remains one of the most common malignancies in the world. Nowadays, the most common lung cancer is non-small cell lung cancer (NSCLC), namely, adenocarcinoma, squamous cell carcinoma, and large cell lung carcinoma. Epigenetic alterations that refer to DNA methylation, histone modifications, and noncoding RNA expression, are now suggested to drive the genesis and development of NSCLC. Additionally, inflammation-related tumorigenesis also plays a vital role in cancer research and efforts have been attempted to reverse such condition. During the occurrence and development of inflammatory diseases, the immune component of inflammation may cause epigenetic changes, but it is not always certain whether the immune component itself or the stimulated host cells cause epigenetic changes. Moreover, the links between epigenetic alterations and cancer-related inflammation and their influences on the human cancer are not clear so far. Therefore, the connection between epigenetic drivers, inflammation, and NSCLC will be summarized. Investigation on such topic is most likely to shed light on the molecular and immunological mechanisms of epigenetic and inflammatory factors and promote the application of epigenetics in the innovative diagnostic and therapeutic strategies for NSCLC.