Chromatin regulators drive cancer epigenetic changes, and lncRNA can play an important role in epigenetic changes as chromatin regulators. We used univariate Cox, LASSO, and multivariate Cox regression analysis to select epigenetic-associated lncRNA signatures. Twenty-five epigenetic-associated lncRNA signatures (CELncSig) were identified to establish the immune prognostic model. According to Kaplan-Meier analysis, the overall survival of the high-risk group was significantly lower than the low-risk group. Receiver operating characteristic (ROC) curves, C-index, survival curve, nomogram, and principal component analysis (PCA) were performed to validate the risk model. In GO/KEGG analysis, differentially expressed lncRNAs were correlated with the PI3K−Akt pathway, suggesting that they were highly associated with the metastasis of LUAD. Interestingly, in the immune escape analysis, the TIDE score was lower, and the possibility of immune dysfunction is also slighter in the high-risk group, which means they still have the potential to receive immunotherapy. And CELncsig is highly correlated with immune pathways T_cell_co-inhibition and Check-point. Also, the IMvigor210 cohort analysis indicated that our risk-scoring model has significant potential clinical application value in lung cancer immunotherapy. And we also screened out ten potential chemotherapy agents using the ‘pRRophetic’ package.