In this study, we found that USP24 increased IL-6 expression by decreasing the stability of DNMT1 by stabilizing β-TrCP in lung cancer cells and increasing the stability of p300 in both lung cancer cells and M2 macrophages, thereby resulting in the acetylation of histone H3 and demethylation of the IL-6 promoter, respectively. Here, EP300 is linked to lung cancer.